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Akihiro Funakoshi - One of the best experts on this subject based on the ideXlab platform.

  • disturbAnce of response to Acute thermAl pAin in nAturAlly occurring Cholecystokinin A Receptor gene knockout otsukA long evAns tokushimA fAtty oletf rAts
    Journal of Pharmacological Sciences, 2006
    Co-Authors: Kyoko Miyasaka, Shigeki Nomoto, Minoru Ohta, Setsuko Kanai, Takao Kaneko, Shoichi Tahara, Akihiro Funakoshi
    Abstract:

    OtsukA Long-EvAns TokushimA FAtty (OLETF) rAts lAck Cholecystokinin-A Receptor (CCK-AR) becAuse of A genetic AbnormAlity. We observed thAt body temperAture homeostAsis in response to chAnges in Ambient temperAture wAs deteriorAted in OLETF rAts, while the functions of the signAl outputs from the hypothAlAmus to effectors were not impAired. DeteriorAted homeostAsis wAs Also seen in CCK-AR deficient (-/-) mice. In the present study, we exAmined whether the sensory pAthwAy involved in trAnsmitting signAls About temperAture from the skin to the brAin wAs impAired in OLETF rAts. To elucidAte the involvement of CCK-AR function, we conducted the sAme experiment in CCK-AR(-/-) mice. Responses to thermAl pAin were Assessed using the HArgreAves' plAntAr test AppArAtus. Shortening of withdrAwAl lAtency wAs observed in OLETF rAts compAred to control rAts, indicAting thermAl hyperAlgesiA. BehAviorAl responses following pAw withdrAwAl were disturbed in OLETF rAts. The 5-hydroxytryptAmine (5-HT) And 5-hydroxyindole Acetic Acid contents in the hippocAmpus And frontAl cortex of OLETF rAts were significAntly higher thAn in those of the controls. CCK-AR(-/-) mice did not show Any differences from wild-type mice. In conclusion, OLETF rAts showed thermAl hyperAlgesiA And disturbed responses to thermAl pAin, And An AlterAtion of 5-HT function might hAve A role in this disturbAnce.

  • differences in ethAnol ingestion between Cholecystokinin A Receptor deficient And b Receptor deficient mice
    Alcohol and Alcoholism, 2005
    Co-Authors: Kyoko Miyasaka, Minoru Ohta, Setsuko Kanai, Hiroko Hosoya, Saeko Takano, Ayako Sekime, Toshimitsu Matsui, Akihiro Funakoshi
    Abstract:

    Aims: Cholecystokinin (CCK) modulAtes dopAmine releAse in the nucleus Accumbens through the CCK-A Receptor (CCK-AR). The dopAminergic neurotrAnsmission between the ventrAl tegmentAl AreA And the limbic forebrAin is A criticAl neurobiologicAl component of Alcohol And drug self-AdministrAtion. BAsed on the evidence of interAction between CCK And dopAmine, we hAd found previously thAt the CCK-AR gene �81A/G polymorphism wAs AssociAted with Alcohol dependence. Since the precise mechAnism underlying this AssociAtion hAs not been elucidAted, the role of CCK-AR in ethAnol ingestion wAs exAmined using CCK-AR gene deficient (�/�) mice And compAred with those of CCK-BR(�/�) And wild-type mice. Methods: The two-bottle choice protocol wAs conducted And the righting reflex wAs exAmined in these three genotypes. Furthermore, the protein level of dopAmine 2 Receptor (D2R) in the nucleus Accumbens wAs determined by western blotting. Results: CCK-AR(�/�) mice consumed more ethAnol thAn CCK-BR(�/�) And wild-type mice, And showed no Aversion to high concentrAtions of ethAnol solution. However, the difference wAs ActuAlly in the totAl fluid consumption And Alcohol preference remAined unchAnged, indicAting thAt the differences were not specific to Alcohol. BehAviorAl sensitivity to ethAnol, exAmined using the righting reflex, did not differ significAntly between the groups. D2R expression in the nucleus Accumbens wAs significAntly lower in the CCK-BR(�/�) mice And wAs significAntly higher in CCK-AR(�/�) mice thAn in wild-type mice. Conclusions: VoluntAry ingestion of ethAnol differed between CCK-AR(�/�) And CCK-BR(�/�) mice. The difference might be AttributAble in pArt to the different levels of D2R expression in the nucleus Accumbens.

  • Cholecystokinin A Receptor gene promoter polymorphism And intelligence.
    Annals of epidemiology, 2005
    Co-Authors: Hiroshi Shimokata, Kyoko Miyasaka, Fujiko Ando, Naoakira Niino, Akihiro Funakoshi
    Abstract:

    Purpose To study the AssociAtion between Cholecystokinin A Receptor (CCKAR) genotypes And intelligence in community-living men And women. Method Subjects were 2251 community-dwelling JApAnese men And women Aged 40 to 79 yeArs. The CCKAR gene promoter polymorphisms A -81 G And G -128 T were determined. Intelligence wAs Assessed by JApAnese Wechsler Adult Intelligence ScAles – Revised Short Forms (JWAIS-R SF). The difference in intelligence between wild type And mutAtion wAs tested. Results There were no subjects with AA / GT , AA / TT , or AG / TT genotypic combinAtions. Both A -81 G And G -128 T genotypes were relAted to intelligence quotient (IQ) estimAted by JWAIS-R SF. The meAn And SE of IQ levels of subjects with the wild-type Allele And the mutAtion Allele At nucleotide -128 were 103.4 ± 0.3 And 101.6 ± 0.6, respectively. There wAs A significAnt difference in IQ for G -128 T (p = 0.008). The difference in IQ for A -81 G wAs Also significAnt (p = 0.011). The IQ level wAs 103.6 ± 0.4 in the subjects with the wild-type Allele And 102.0 ± 0.5 in the subjects with the mutAtion. Differences in IQ levels by hAplotypes for combinAtions of A -81 G / G -128 T were exAmined. IQ significAntly decreAsed with An increAsing number of mutAtion Alleles (p = 0.018). Conclusion There were stAtisticAlly significAnt differences in IQ for CCKAR gene promoter polymorphisms A -81 G And G -128 T in community-living JApAnese.

  • AssociAtion of Cholecystokinin A Receptor gene polymorphism with cholelithiAsis And the moleculAr mechAnisms of this polymorphism.
    Journal of Gastroenterology, 2002
    Co-Authors: Kyoko Miyasaka, Yutaka Takata, Akihiro Funakoshi
    Abstract:

    BAckground. The etiology of gAllstone formAtion is multifActoriAl, And genetic fActors Are involved. The genetic vAriAtions of Cholecystokinin A Receptor (CCK-AR) in pAtients hAving gAllstones And the moleculAr mechAnisms of this polymorhpism were exAmined. The involvement of CCK-AR in gAllstone formAtion wAs confirmed using CCK-AR gene knockout mice. Methods. CCK-AR gene expression wAs determined by Northern trAnsfer AnAlysis in gAllblAdders with or without gAllstones. Genetic vAriAtions were determined by Southern blot And by direct sequencing. MoleculAr mechAnisms in terms of the trAnscriptionAl Activity And methylAtion stAtus were exAmined. FinAlly, we investigAted whether gAllstone formAtion wAs enhAnced in CCK-AR gene knockout mice. Results. The gene expression of CCK-AR wAs significAntly decreAsed in gAllblAdders with gAllstones compAred to those without gAllstones. No genetic vAriAtions were detected in the coding region, but two sequence vAriAtions were detected in the promoter region in gAllstone pAtients. However, no significAnt differences were found for the promoter Activities of polymorphic promoter constructs. In contrAst, less methylAtion in the promoter region wAs relAted to substAntiAl expression of the CCK-AR gene. GAllstone formAtion wAs enhAnced in CCK-AR gene knockout mice. The homozygote (GG/TT) polymorphism of the CCK-AR gene showed A significAntly higher percentAge of body fAt. Conclusions. DeteriorAting gAllblAdder contrActions, possibly induced by AlterAtions in the CCK-AR gene, As well As CCK-AR gene polymorphism, promoted gAllstone formAtion.

  • different effects of orAl AdministrAtion of synthetic trypsin inhibitor on the pAncreAs between Cholecystokinin A Receptor gene knockout mice And wild type mice
    Japanese Journal of Pharmacology, 2002
    Co-Authors: Norikazu Sato, Akihiro Funakoshi, Minoru Ohta, Setsuko Kanai, Shinji Suzuki, Tetsuo Noda, Atsuo Jimi, Souichi Takiguchi, Kyoko Miyasaka
    Abstract:

    The synthetic trypsin inhibitor cAmostAt hAs been used for the treAtment of Acute And chronic pAncreAtitis in JApAn bAsed on the evidences obtAined from A rAt experimentAl model. However, rAts differ from other rodents And from humAns in terms of lAcking A gAllblAdder And no response of pAncreAtic bicArbonAte secretion to Cholecystokinin (CCK). In the present study, we determined whether orAl AdministrAtion of cAmostAt showed A trophic effect in mice As observed in rAts And whether the trophic effect, if substAntiAl, wAs mediAted viA the CCK-A Receptor, using CCK-A Receptor gene tArgeting mice. The chow contAining 0.1% cAmostAt wAs fed to 8-month-old mice. Three- And seven-dAy treAtments with cAmostAt did not Affect pAncreAtic wet weight in CCK-A Receptor (+/-) mice. After 14-dAy treAtment, the rAtio of pAncreAtic wet weight/body weight wAs significAntly lower in CCK-A Receptor (-/-) thAn (+/+) mice. The protein And chymotrypsin contents were lower And AmylAse content wAs higher in CCK-A Receptor (-/-) mice, compAred to (+/+) mice. No pAthologicAl findings were observed by histologicAl exAminAtion. CAmostAt hAs A trophic effect on the pAncreAs in mice And this effect is mediAted viA the CCK-A Receptor, but is less potent thAn in rAts.

Kyoko Miyasaka - One of the best experts on this subject based on the ideXlab platform.

  • disturbAnce of response to Acute thermAl pAin in nAturAlly occurring Cholecystokinin A Receptor gene knockout otsukA long evAns tokushimA fAtty oletf rAts
    Journal of Pharmacological Sciences, 2006
    Co-Authors: Kyoko Miyasaka, Shigeki Nomoto, Minoru Ohta, Setsuko Kanai, Takao Kaneko, Shoichi Tahara, Akihiro Funakoshi
    Abstract:

    OtsukA Long-EvAns TokushimA FAtty (OLETF) rAts lAck Cholecystokinin-A Receptor (CCK-AR) becAuse of A genetic AbnormAlity. We observed thAt body temperAture homeostAsis in response to chAnges in Ambient temperAture wAs deteriorAted in OLETF rAts, while the functions of the signAl outputs from the hypothAlAmus to effectors were not impAired. DeteriorAted homeostAsis wAs Also seen in CCK-AR deficient (-/-) mice. In the present study, we exAmined whether the sensory pAthwAy involved in trAnsmitting signAls About temperAture from the skin to the brAin wAs impAired in OLETF rAts. To elucidAte the involvement of CCK-AR function, we conducted the sAme experiment in CCK-AR(-/-) mice. Responses to thermAl pAin were Assessed using the HArgreAves' plAntAr test AppArAtus. Shortening of withdrAwAl lAtency wAs observed in OLETF rAts compAred to control rAts, indicAting thermAl hyperAlgesiA. BehAviorAl responses following pAw withdrAwAl were disturbed in OLETF rAts. The 5-hydroxytryptAmine (5-HT) And 5-hydroxyindole Acetic Acid contents in the hippocAmpus And frontAl cortex of OLETF rAts were significAntly higher thAn in those of the controls. CCK-AR(-/-) mice did not show Any differences from wild-type mice. In conclusion, OLETF rAts showed thermAl hyperAlgesiA And disturbed responses to thermAl pAin, And An AlterAtion of 5-HT function might hAve A role in this disturbAnce.

  • differences in ethAnol ingestion between Cholecystokinin A Receptor deficient And b Receptor deficient mice
    Alcohol and Alcoholism, 2005
    Co-Authors: Kyoko Miyasaka, Minoru Ohta, Setsuko Kanai, Hiroko Hosoya, Saeko Takano, Ayako Sekime, Toshimitsu Matsui, Akihiro Funakoshi
    Abstract:

    Aims: Cholecystokinin (CCK) modulAtes dopAmine releAse in the nucleus Accumbens through the CCK-A Receptor (CCK-AR). The dopAminergic neurotrAnsmission between the ventrAl tegmentAl AreA And the limbic forebrAin is A criticAl neurobiologicAl component of Alcohol And drug self-AdministrAtion. BAsed on the evidence of interAction between CCK And dopAmine, we hAd found previously thAt the CCK-AR gene �81A/G polymorphism wAs AssociAted with Alcohol dependence. Since the precise mechAnism underlying this AssociAtion hAs not been elucidAted, the role of CCK-AR in ethAnol ingestion wAs exAmined using CCK-AR gene deficient (�/�) mice And compAred with those of CCK-BR(�/�) And wild-type mice. Methods: The two-bottle choice protocol wAs conducted And the righting reflex wAs exAmined in these three genotypes. Furthermore, the protein level of dopAmine 2 Receptor (D2R) in the nucleus Accumbens wAs determined by western blotting. Results: CCK-AR(�/�) mice consumed more ethAnol thAn CCK-BR(�/�) And wild-type mice, And showed no Aversion to high concentrAtions of ethAnol solution. However, the difference wAs ActuAlly in the totAl fluid consumption And Alcohol preference remAined unchAnged, indicAting thAt the differences were not specific to Alcohol. BehAviorAl sensitivity to ethAnol, exAmined using the righting reflex, did not differ significAntly between the groups. D2R expression in the nucleus Accumbens wAs significAntly lower in the CCK-BR(�/�) mice And wAs significAntly higher in CCK-AR(�/�) mice thAn in wild-type mice. Conclusions: VoluntAry ingestion of ethAnol differed between CCK-AR(�/�) And CCK-BR(�/�) mice. The difference might be AttributAble in pArt to the different levels of D2R expression in the nucleus Accumbens.

  • Cholecystokinin A Receptor gene promoter polymorphism And intelligence.
    Annals of epidemiology, 2005
    Co-Authors: Hiroshi Shimokata, Kyoko Miyasaka, Fujiko Ando, Naoakira Niino, Akihiro Funakoshi
    Abstract:

    Purpose To study the AssociAtion between Cholecystokinin A Receptor (CCKAR) genotypes And intelligence in community-living men And women. Method Subjects were 2251 community-dwelling JApAnese men And women Aged 40 to 79 yeArs. The CCKAR gene promoter polymorphisms A -81 G And G -128 T were determined. Intelligence wAs Assessed by JApAnese Wechsler Adult Intelligence ScAles – Revised Short Forms (JWAIS-R SF). The difference in intelligence between wild type And mutAtion wAs tested. Results There were no subjects with AA / GT , AA / TT , or AG / TT genotypic combinAtions. Both A -81 G And G -128 T genotypes were relAted to intelligence quotient (IQ) estimAted by JWAIS-R SF. The meAn And SE of IQ levels of subjects with the wild-type Allele And the mutAtion Allele At nucleotide -128 were 103.4 ± 0.3 And 101.6 ± 0.6, respectively. There wAs A significAnt difference in IQ for G -128 T (p = 0.008). The difference in IQ for A -81 G wAs Also significAnt (p = 0.011). The IQ level wAs 103.6 ± 0.4 in the subjects with the wild-type Allele And 102.0 ± 0.5 in the subjects with the mutAtion. Differences in IQ levels by hAplotypes for combinAtions of A -81 G / G -128 T were exAmined. IQ significAntly decreAsed with An increAsing number of mutAtion Alleles (p = 0.018). Conclusion There were stAtisticAlly significAnt differences in IQ for CCKAR gene promoter polymorphisms A -81 G And G -128 T in community-living JApAnese.

  • lAck of Cholecystokinin A Receptor enhAnced gAllstone formAtion A study in cck A Receptor gene knockout mice
    Digestive Diseases and Sciences, 2003
    Co-Authors: Norikazu Sato, Kyoko Miyasaka, Minoru Ohta, Setsuko Kanai, Shinji Suzuki, Takako Kawanami, Yuki Yoshida, Soichi Takiguchi, Tetsuo Noda, Yutaka Takata
    Abstract:

    The etiology of gAllstones is multifActoriAl, with interActions between genes And the environment. We generAted Cholecystokinin (CCK) -A Receptor (R)-deficient (-/-) mice And found thAt CCK did not produce gAllblAdder contrAction in CCK-AR(-/-) mice. The purpose of this study wAs to identify the role of CCK-AR on gAllstone formAtion. Age-mAtched CCK-AR gene (+/+) And (-/-) progenies were used. Sludge And gAllstone formAtion, As well As plAsmA cholesterol levels, were meAsured At 12 And 24 months of Age. Sludge And gAllstone formAtion were significAntly higher in CCK-AR(-/-) mice thAn in CCK-AR(+/+) mice At 12 And 24 months of Age, Although these were not different between 12 And 24 months of Age. The plAsmA cholesterol levels, dAily food intAke, And body weight were not significAntly different between CCK-AR(+/+) And (-/-) mice. Sludge And gAllstone formAtion were not observed At 6 months of Age. In conclusion, deteriorAted gAllblAdder contrAction due to A lAck of CCK-AR fAvored gAllstone formAtion After the middle Age of life.

  • AssociAtion of Cholecystokinin A Receptor gene polymorphism with cholelithiAsis And the moleculAr mechAnisms of this polymorphism.
    Journal of Gastroenterology, 2002
    Co-Authors: Kyoko Miyasaka, Yutaka Takata, Akihiro Funakoshi
    Abstract:

    BAckground. The etiology of gAllstone formAtion is multifActoriAl, And genetic fActors Are involved. The genetic vAriAtions of Cholecystokinin A Receptor (CCK-AR) in pAtients hAving gAllstones And the moleculAr mechAnisms of this polymorhpism were exAmined. The involvement of CCK-AR in gAllstone formAtion wAs confirmed using CCK-AR gene knockout mice. Methods. CCK-AR gene expression wAs determined by Northern trAnsfer AnAlysis in gAllblAdders with or without gAllstones. Genetic vAriAtions were determined by Southern blot And by direct sequencing. MoleculAr mechAnisms in terms of the trAnscriptionAl Activity And methylAtion stAtus were exAmined. FinAlly, we investigAted whether gAllstone formAtion wAs enhAnced in CCK-AR gene knockout mice. Results. The gene expression of CCK-AR wAs significAntly decreAsed in gAllblAdders with gAllstones compAred to those without gAllstones. No genetic vAriAtions were detected in the coding region, but two sequence vAriAtions were detected in the promoter region in gAllstone pAtients. However, no significAnt differences were found for the promoter Activities of polymorphic promoter constructs. In contrAst, less methylAtion in the promoter region wAs relAted to substAntiAl expression of the CCK-AR gene. GAllstone formAtion wAs enhAnced in CCK-AR gene knockout mice. The homozygote (GG/TT) polymorphism of the CCK-AR gene showed A significAntly higher percentAge of body fAt. Conclusions. DeteriorAting gAllblAdder contrActions, possibly induced by AlterAtions in the CCK-AR gene, As well As CCK-AR gene polymorphism, promoted gAllstone formAtion.

Minoru Ohta - One of the best experts on this subject based on the ideXlab platform.

  • disturbAnce of response to Acute thermAl pAin in nAturAlly occurring Cholecystokinin A Receptor gene knockout otsukA long evAns tokushimA fAtty oletf rAts
    Journal of Pharmacological Sciences, 2006
    Co-Authors: Kyoko Miyasaka, Shigeki Nomoto, Minoru Ohta, Setsuko Kanai, Takao Kaneko, Shoichi Tahara, Akihiro Funakoshi
    Abstract:

    OtsukA Long-EvAns TokushimA FAtty (OLETF) rAts lAck Cholecystokinin-A Receptor (CCK-AR) becAuse of A genetic AbnormAlity. We observed thAt body temperAture homeostAsis in response to chAnges in Ambient temperAture wAs deteriorAted in OLETF rAts, while the functions of the signAl outputs from the hypothAlAmus to effectors were not impAired. DeteriorAted homeostAsis wAs Also seen in CCK-AR deficient (-/-) mice. In the present study, we exAmined whether the sensory pAthwAy involved in trAnsmitting signAls About temperAture from the skin to the brAin wAs impAired in OLETF rAts. To elucidAte the involvement of CCK-AR function, we conducted the sAme experiment in CCK-AR(-/-) mice. Responses to thermAl pAin were Assessed using the HArgreAves' plAntAr test AppArAtus. Shortening of withdrAwAl lAtency wAs observed in OLETF rAts compAred to control rAts, indicAting thermAl hyperAlgesiA. BehAviorAl responses following pAw withdrAwAl were disturbed in OLETF rAts. The 5-hydroxytryptAmine (5-HT) And 5-hydroxyindole Acetic Acid contents in the hippocAmpus And frontAl cortex of OLETF rAts were significAntly higher thAn in those of the controls. CCK-AR(-/-) mice did not show Any differences from wild-type mice. In conclusion, OLETF rAts showed thermAl hyperAlgesiA And disturbed responses to thermAl pAin, And An AlterAtion of 5-HT function might hAve A role in this disturbAnce.

  • differences in ethAnol ingestion between Cholecystokinin A Receptor deficient And b Receptor deficient mice
    Alcohol and Alcoholism, 2005
    Co-Authors: Kyoko Miyasaka, Minoru Ohta, Setsuko Kanai, Hiroko Hosoya, Saeko Takano, Ayako Sekime, Toshimitsu Matsui, Akihiro Funakoshi
    Abstract:

    Aims: Cholecystokinin (CCK) modulAtes dopAmine releAse in the nucleus Accumbens through the CCK-A Receptor (CCK-AR). The dopAminergic neurotrAnsmission between the ventrAl tegmentAl AreA And the limbic forebrAin is A criticAl neurobiologicAl component of Alcohol And drug self-AdministrAtion. BAsed on the evidence of interAction between CCK And dopAmine, we hAd found previously thAt the CCK-AR gene �81A/G polymorphism wAs AssociAted with Alcohol dependence. Since the precise mechAnism underlying this AssociAtion hAs not been elucidAted, the role of CCK-AR in ethAnol ingestion wAs exAmined using CCK-AR gene deficient (�/�) mice And compAred with those of CCK-BR(�/�) And wild-type mice. Methods: The two-bottle choice protocol wAs conducted And the righting reflex wAs exAmined in these three genotypes. Furthermore, the protein level of dopAmine 2 Receptor (D2R) in the nucleus Accumbens wAs determined by western blotting. Results: CCK-AR(�/�) mice consumed more ethAnol thAn CCK-BR(�/�) And wild-type mice, And showed no Aversion to high concentrAtions of ethAnol solution. However, the difference wAs ActuAlly in the totAl fluid consumption And Alcohol preference remAined unchAnged, indicAting thAt the differences were not specific to Alcohol. BehAviorAl sensitivity to ethAnol, exAmined using the righting reflex, did not differ significAntly between the groups. D2R expression in the nucleus Accumbens wAs significAntly lower in the CCK-BR(�/�) mice And wAs significAntly higher in CCK-AR(�/�) mice thAn in wild-type mice. Conclusions: VoluntAry ingestion of ethAnol differed between CCK-AR(�/�) And CCK-BR(�/�) mice. The difference might be AttributAble in pArt to the different levels of D2R expression in the nucleus Accumbens.

  • lAck of Cholecystokinin A Receptor enhAnced gAllstone formAtion A study in cck A Receptor gene knockout mice
    Digestive Diseases and Sciences, 2003
    Co-Authors: Norikazu Sato, Kyoko Miyasaka, Minoru Ohta, Setsuko Kanai, Shinji Suzuki, Takako Kawanami, Yuki Yoshida, Soichi Takiguchi, Tetsuo Noda, Yutaka Takata
    Abstract:

    The etiology of gAllstones is multifActoriAl, with interActions between genes And the environment. We generAted Cholecystokinin (CCK) -A Receptor (R)-deficient (-/-) mice And found thAt CCK did not produce gAllblAdder contrAction in CCK-AR(-/-) mice. The purpose of this study wAs to identify the role of CCK-AR on gAllstone formAtion. Age-mAtched CCK-AR gene (+/+) And (-/-) progenies were used. Sludge And gAllstone formAtion, As well As plAsmA cholesterol levels, were meAsured At 12 And 24 months of Age. Sludge And gAllstone formAtion were significAntly higher in CCK-AR(-/-) mice thAn in CCK-AR(+/+) mice At 12 And 24 months of Age, Although these were not different between 12 And 24 months of Age. The plAsmA cholesterol levels, dAily food intAke, And body weight were not significAntly different between CCK-AR(+/+) And (-/-) mice. Sludge And gAllstone formAtion were not observed At 6 months of Age. In conclusion, deteriorAted gAllblAdder contrAction due to A lAck of CCK-AR fAvored gAllstone formAtion After the middle Age of life.

  • different effects of orAl AdministrAtion of synthetic trypsin inhibitor on the pAncreAs between Cholecystokinin A Receptor gene knockout mice And wild type mice
    Japanese Journal of Pharmacology, 2002
    Co-Authors: Norikazu Sato, Akihiro Funakoshi, Minoru Ohta, Setsuko Kanai, Shinji Suzuki, Tetsuo Noda, Atsuo Jimi, Souichi Takiguchi, Kyoko Miyasaka
    Abstract:

    The synthetic trypsin inhibitor cAmostAt hAs been used for the treAtment of Acute And chronic pAncreAtitis in JApAn bAsed on the evidences obtAined from A rAt experimentAl model. However, rAts differ from other rodents And from humAns in terms of lAcking A gAllblAdder And no response of pAncreAtic bicArbonAte secretion to Cholecystokinin (CCK). In the present study, we determined whether orAl AdministrAtion of cAmostAt showed A trophic effect in mice As observed in rAts And whether the trophic effect, if substAntiAl, wAs mediAted viA the CCK-A Receptor, using CCK-A Receptor gene tArgeting mice. The chow contAining 0.1% cAmostAt wAs fed to 8-month-old mice. Three- And seven-dAy treAtments with cAmostAt did not Affect pAncreAtic wet weight in CCK-A Receptor (+/-) mice. After 14-dAy treAtment, the rAtio of pAncreAtic wet weight/body weight wAs significAntly lower in CCK-A Receptor (-/-) thAn (+/+) mice. The protein And chymotrypsin contents were lower And AmylAse content wAs higher in CCK-A Receptor (-/-) mice, compAred to (+/+) mice. No pAthologicAl findings were observed by histologicAl exAminAtion. CAmostAt hAs A trophic effect on the pAncreAs in mice And this effect is mediAted viA the CCK-A Receptor, but is less potent thAn in rAts.

  • overexpression of Cholecystokinin b gAstrin Receptor gene in the stomAch of nAturAlly occurring Cholecystokinin A Receptor gene knockout rAts
    Digestion, 1998
    Co-Authors: Kyoko Miyasaka, Minoru Ohta, Setsuko Kanai, Atsuo Jimi, Akira Kono, Akihiro Funakoshi
    Abstract:

    We exAmined the Cholecystokinin (CCK)-B/gAstrin Receptor, H+/K+-ATPAse And somAtostAtin gene expression, the histology And immunohistochemistry of gAstrin And somAtostAtin of the

Setsuko Kanai - One of the best experts on this subject based on the ideXlab platform.

  • disturbAnce of response to Acute thermAl pAin in nAturAlly occurring Cholecystokinin A Receptor gene knockout otsukA long evAns tokushimA fAtty oletf rAts
    Journal of Pharmacological Sciences, 2006
    Co-Authors: Kyoko Miyasaka, Shigeki Nomoto, Minoru Ohta, Setsuko Kanai, Takao Kaneko, Shoichi Tahara, Akihiro Funakoshi
    Abstract:

    OtsukA Long-EvAns TokushimA FAtty (OLETF) rAts lAck Cholecystokinin-A Receptor (CCK-AR) becAuse of A genetic AbnormAlity. We observed thAt body temperAture homeostAsis in response to chAnges in Ambient temperAture wAs deteriorAted in OLETF rAts, while the functions of the signAl outputs from the hypothAlAmus to effectors were not impAired. DeteriorAted homeostAsis wAs Also seen in CCK-AR deficient (-/-) mice. In the present study, we exAmined whether the sensory pAthwAy involved in trAnsmitting signAls About temperAture from the skin to the brAin wAs impAired in OLETF rAts. To elucidAte the involvement of CCK-AR function, we conducted the sAme experiment in CCK-AR(-/-) mice. Responses to thermAl pAin were Assessed using the HArgreAves' plAntAr test AppArAtus. Shortening of withdrAwAl lAtency wAs observed in OLETF rAts compAred to control rAts, indicAting thermAl hyperAlgesiA. BehAviorAl responses following pAw withdrAwAl were disturbed in OLETF rAts. The 5-hydroxytryptAmine (5-HT) And 5-hydroxyindole Acetic Acid contents in the hippocAmpus And frontAl cortex of OLETF rAts were significAntly higher thAn in those of the controls. CCK-AR(-/-) mice did not show Any differences from wild-type mice. In conclusion, OLETF rAts showed thermAl hyperAlgesiA And disturbed responses to thermAl pAin, And An AlterAtion of 5-HT function might hAve A role in this disturbAnce.

  • differences in ethAnol ingestion between Cholecystokinin A Receptor deficient And b Receptor deficient mice
    Alcohol and Alcoholism, 2005
    Co-Authors: Kyoko Miyasaka, Minoru Ohta, Setsuko Kanai, Hiroko Hosoya, Saeko Takano, Ayako Sekime, Toshimitsu Matsui, Akihiro Funakoshi
    Abstract:

    Aims: Cholecystokinin (CCK) modulAtes dopAmine releAse in the nucleus Accumbens through the CCK-A Receptor (CCK-AR). The dopAminergic neurotrAnsmission between the ventrAl tegmentAl AreA And the limbic forebrAin is A criticAl neurobiologicAl component of Alcohol And drug self-AdministrAtion. BAsed on the evidence of interAction between CCK And dopAmine, we hAd found previously thAt the CCK-AR gene �81A/G polymorphism wAs AssociAted with Alcohol dependence. Since the precise mechAnism underlying this AssociAtion hAs not been elucidAted, the role of CCK-AR in ethAnol ingestion wAs exAmined using CCK-AR gene deficient (�/�) mice And compAred with those of CCK-BR(�/�) And wild-type mice. Methods: The two-bottle choice protocol wAs conducted And the righting reflex wAs exAmined in these three genotypes. Furthermore, the protein level of dopAmine 2 Receptor (D2R) in the nucleus Accumbens wAs determined by western blotting. Results: CCK-AR(�/�) mice consumed more ethAnol thAn CCK-BR(�/�) And wild-type mice, And showed no Aversion to high concentrAtions of ethAnol solution. However, the difference wAs ActuAlly in the totAl fluid consumption And Alcohol preference remAined unchAnged, indicAting thAt the differences were not specific to Alcohol. BehAviorAl sensitivity to ethAnol, exAmined using the righting reflex, did not differ significAntly between the groups. D2R expression in the nucleus Accumbens wAs significAntly lower in the CCK-BR(�/�) mice And wAs significAntly higher in CCK-AR(�/�) mice thAn in wild-type mice. Conclusions: VoluntAry ingestion of ethAnol differed between CCK-AR(�/�) And CCK-BR(�/�) mice. The difference might be AttributAble in pArt to the different levels of D2R expression in the nucleus Accumbens.

  • lAck of Cholecystokinin A Receptor enhAnced gAllstone formAtion A study in cck A Receptor gene knockout mice
    Digestive Diseases and Sciences, 2003
    Co-Authors: Norikazu Sato, Kyoko Miyasaka, Minoru Ohta, Setsuko Kanai, Shinji Suzuki, Takako Kawanami, Yuki Yoshida, Soichi Takiguchi, Tetsuo Noda, Yutaka Takata
    Abstract:

    The etiology of gAllstones is multifActoriAl, with interActions between genes And the environment. We generAted Cholecystokinin (CCK) -A Receptor (R)-deficient (-/-) mice And found thAt CCK did not produce gAllblAdder contrAction in CCK-AR(-/-) mice. The purpose of this study wAs to identify the role of CCK-AR on gAllstone formAtion. Age-mAtched CCK-AR gene (+/+) And (-/-) progenies were used. Sludge And gAllstone formAtion, As well As plAsmA cholesterol levels, were meAsured At 12 And 24 months of Age. Sludge And gAllstone formAtion were significAntly higher in CCK-AR(-/-) mice thAn in CCK-AR(+/+) mice At 12 And 24 months of Age, Although these were not different between 12 And 24 months of Age. The plAsmA cholesterol levels, dAily food intAke, And body weight were not significAntly different between CCK-AR(+/+) And (-/-) mice. Sludge And gAllstone formAtion were not observed At 6 months of Age. In conclusion, deteriorAted gAllblAdder contrAction due to A lAck of CCK-AR fAvored gAllstone formAtion After the middle Age of life.

  • different effects of orAl AdministrAtion of synthetic trypsin inhibitor on the pAncreAs between Cholecystokinin A Receptor gene knockout mice And wild type mice
    Japanese Journal of Pharmacology, 2002
    Co-Authors: Norikazu Sato, Akihiro Funakoshi, Minoru Ohta, Setsuko Kanai, Shinji Suzuki, Tetsuo Noda, Atsuo Jimi, Souichi Takiguchi, Kyoko Miyasaka
    Abstract:

    The synthetic trypsin inhibitor cAmostAt hAs been used for the treAtment of Acute And chronic pAncreAtitis in JApAn bAsed on the evidences obtAined from A rAt experimentAl model. However, rAts differ from other rodents And from humAns in terms of lAcking A gAllblAdder And no response of pAncreAtic bicArbonAte secretion to Cholecystokinin (CCK). In the present study, we determined whether orAl AdministrAtion of cAmostAt showed A trophic effect in mice As observed in rAts And whether the trophic effect, if substAntiAl, wAs mediAted viA the CCK-A Receptor, using CCK-A Receptor gene tArgeting mice. The chow contAining 0.1% cAmostAt wAs fed to 8-month-old mice. Three- And seven-dAy treAtments with cAmostAt did not Affect pAncreAtic wet weight in CCK-A Receptor (+/-) mice. After 14-dAy treAtment, the rAtio of pAncreAtic wet weight/body weight wAs significAntly lower in CCK-A Receptor (-/-) thAn (+/+) mice. The protein And chymotrypsin contents were lower And AmylAse content wAs higher in CCK-A Receptor (-/-) mice, compAred to (+/+) mice. No pAthologicAl findings were observed by histologicAl exAminAtion. CAmostAt hAs A trophic effect on the pAncreAs in mice And this effect is mediAted viA the CCK-A Receptor, but is less potent thAn in rAts.

  • overexpression of Cholecystokinin b gAstrin Receptor gene in the stomAch of nAturAlly occurring Cholecystokinin A Receptor gene knockout rAts
    Digestion, 1998
    Co-Authors: Kyoko Miyasaka, Minoru Ohta, Setsuko Kanai, Atsuo Jimi, Akira Kono, Akihiro Funakoshi
    Abstract:

    We exAmined the Cholecystokinin (CCK)-B/gAstrin Receptor, H+/K+-ATPAse And somAtostAtin gene expression, the histology And immunohistochemistry of gAstrin And somAtostAtin of the

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  • lAck of Cholecystokinin A Receptor enhAnced gAllstone formAtion A study in cck A Receptor gene knockout mice
    Digestive Diseases and Sciences, 2003
    Co-Authors: Norikazu Sato, Kyoko Miyasaka, Minoru Ohta, Setsuko Kanai, Shinji Suzuki, Takako Kawanami, Yuki Yoshida, Soichi Takiguchi, Tetsuo Noda, Yutaka Takata
    Abstract:

    The etiology of gAllstones is multifActoriAl, with interActions between genes And the environment. We generAted Cholecystokinin (CCK) -A Receptor (R)-deficient (-/-) mice And found thAt CCK did not produce gAllblAdder contrAction in CCK-AR(-/-) mice. The purpose of this study wAs to identify the role of CCK-AR on gAllstone formAtion. Age-mAtched CCK-AR gene (+/+) And (-/-) progenies were used. Sludge And gAllstone formAtion, As well As plAsmA cholesterol levels, were meAsured At 12 And 24 months of Age. Sludge And gAllstone formAtion were significAntly higher in CCK-AR(-/-) mice thAn in CCK-AR(+/+) mice At 12 And 24 months of Age, Although these were not different between 12 And 24 months of Age. The plAsmA cholesterol levels, dAily food intAke, And body weight were not significAntly different between CCK-AR(+/+) And (-/-) mice. Sludge And gAllstone formAtion were not observed At 6 months of Age. In conclusion, deteriorAted gAllblAdder contrAction due to A lAck of CCK-AR fAvored gAllstone formAtion After the middle Age of life.

  • AssociAtion of Cholecystokinin A Receptor gene polymorphism with cholelithiAsis And the moleculAr mechAnisms of this polymorphism.
    Journal of Gastroenterology, 2002
    Co-Authors: Kyoko Miyasaka, Yutaka Takata, Akihiro Funakoshi
    Abstract:

    BAckground. The etiology of gAllstone formAtion is multifActoriAl, And genetic fActors Are involved. The genetic vAriAtions of Cholecystokinin A Receptor (CCK-AR) in pAtients hAving gAllstones And the moleculAr mechAnisms of this polymorhpism were exAmined. The involvement of CCK-AR in gAllstone formAtion wAs confirmed using CCK-AR gene knockout mice. Methods. CCK-AR gene expression wAs determined by Northern trAnsfer AnAlysis in gAllblAdders with or without gAllstones. Genetic vAriAtions were determined by Southern blot And by direct sequencing. MoleculAr mechAnisms in terms of the trAnscriptionAl Activity And methylAtion stAtus were exAmined. FinAlly, we investigAted whether gAllstone formAtion wAs enhAnced in CCK-AR gene knockout mice. Results. The gene expression of CCK-AR wAs significAntly decreAsed in gAllblAdders with gAllstones compAred to those without gAllstones. No genetic vAriAtions were detected in the coding region, but two sequence vAriAtions were detected in the promoter region in gAllstone pAtients. However, no significAnt differences were found for the promoter Activities of polymorphic promoter constructs. In contrAst, less methylAtion in the promoter region wAs relAted to substAntiAl expression of the CCK-AR gene. GAllstone formAtion wAs enhAnced in CCK-AR gene knockout mice. The homozygote (GG/TT) polymorphism of the CCK-AR gene showed A significAntly higher percentAge of body fAt. Conclusions. DeteriorAting gAllblAdder contrActions, possibly induced by AlterAtions in the CCK-AR gene, As well As CCK-AR gene polymorphism, promoted gAllstone formAtion.

  • AssociAtion of Cholecystokinin A Receptor gene polymorphism with cholelithiAsis And the moleculAr mechAnisms of this polymorphism.
    Journal of gastroenterology, 2002
    Co-Authors: Kyoko Miyasaka, Yutaka Takata, Akihiro Funakoshi
    Abstract:

    The etiology of gAllstone formAtion is multifActoriAl, And genetic fActors Are involved. The genetic vAriAtions of Cholecystokinin A Receptor (CCK-AR) in pAtients hAving gAllstones And the moleculAr mechAnisms of this polymorhpism were exAmined. The involvement of CCK-AR in gAllstone formAtion wAs confirmed using CCK-AR gene knockout mice. CCK-AR gene expression wAs determined by Northern trAnsfer AnAlysis in gAllblAdders with or without gAllstones. Genetic vAriAtions were determined by Southern blot And by direct sequencing. MoleculAr mechAnisms in terms of the trAnscriptionAl Activity And methylAtion stAtus were exAmined. FinAlly, we investigAted whether gAllstone formAtion wAs enhAnced in CCK-AR gene knockout mice. The gene expression of CCK-AR wAs significAntly decreAsed in gAllblAdders with gAllstones compAred to those without gAllstones. No genetic vAriAtions were detected in the coding region, but two sequence vAriAtions were detected in the promoter region in gAllstone pAtients. However, no significAnt differences were found for the promoter Activities of polymorphic promoter constructs. In contrAst, less methylAtion in the promoter region wAs relAted to substAntiAl expression of the CCK-AR gene. GAllstone formAtion wAs enhAnced in CCK-AR gene knockout mice. The homozygote (GG/TT) polymorphism of the CCK-AR gene showed A significAntly higher percentAge of body fAt. DeteriorAting gAllblAdder contrActions, possibly induced by AlterAtions in the CCK-AR gene, As well As CCK-AR gene polymorphism, promoted gAllstone formAtion.

  • little or no expression of the Cholecystokinin A Receptor gene in the pAncreAs of diAbetic rAts otsukA long evAns tokushimA fAtty oletf rAts
    Biochemical and Biophysical Research Communications, 1994
    Co-Authors: Akihiro Funakoshi, Kyoko Miyasaka, Yutaka Takata, Atsuo Jimi, T Kawanai, Akira Kono
    Abstract:

    Expression of the CCK-A Receptor gene in the pAncreAs And pAncreAtic exocrine function wAs exAmined in diAbetic model rAts (OLETF) At 5 wks of Age. Little or no CCK-A Receptor wAs detected in the pAncreAs of OLETF rAts. PAncreAtic exocrine function in response to exogenous CCK And to bile-pAncreAtic juice diversion (endogenous CCK) wAs impAired in conscious OLETF rAts. The pAncreAtic insulin And protein contents of OLETF (OtsukA Long-EvAns TokushimA FAtty) And control LETO (Long-EvAns TokushimA OtsukA) rAts were not significAntly different. No histologicAl AbnormAlities or expression of pAncreAtitis AssociAted protein (PAP) mRNA wAs detected in the pAncreAs in either group. These results suggest thAt OLETF rAts Are A new experimentAl model for congenitAl deficiency of CCK-A Receptor in the pAncreAs.