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Robert M Weiss - One of the best experts on this subject based on the ideXlab platform.
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Developmental aspects of endothelin receptors in rabbit lower urinary tract.
Neurourology and Urodynamics, 2020Co-Authors: Motoaki Saito, Jamshid Latifpour, Robert M WeissAbstract:Since evidence of development/age-related alterations of endothelin receptors in circulation and respiration systems has been increasing, we attempted to investigate the pharmacological characterization of endothelin receptors in neonatal, premature, and mature male rabbit lower urinary tract. The biochemical properties of ET receptors were examined in the lower urinary tracts of 1-day (neonatal)-, 6-week (premature)-, and 1-year(mature)-old male rabbits with binding technique utilizing [125I]ET-1. The rank orders of the densities (Bmax values) of endothelin receptors in the Bladder Dome, Bladder base, and urethra of different aged rabbits were Bladder Dome, 1 day > 6 week vLs 1 year, Bladder base, 1 day > 6 week vLs 1 year, and urethra, 1 day > 6 week > 1 year. The pharmacological profiles of these binding sites inhibited by various kinds of endothelin receptor compounds showed similar Ki values and similar proportions of endothelin receptor subtypes in the same regions of 1-day-, 6-week-, and 1-year-old animals. Our data clearly demonstrated the presence of regional difference and development-related changes in the density and subtype specificity of endothelin receptors in the lower urinary tract of the male rabbit. Neurourol. Urodynam. 19:71–85, 2000. © 2000 Wiley-Liss, Inc.
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Age-related changes in contractile responses of rabbit lower urinary tract to endothelin.
The Journal of Urology, 2000Co-Authors: Yoshihiro Wada, Motoaki Saito, Zejing Wang, Kazuhiko Nishi, Jamshid Latifpour, Hiromi Sanematsu, Parviz Afiatpour, Robert M WeissAbstract:Purpose: As there are significant amounts of endothelin (ET) receptors in the mammalian urinary tract, we investigated the pharmacological properties and localization of ET receptors in the rabbit lower urinary tract as a function of age.Materials and Methods: The characteristics of ET receptors in Bladder Dome, trigone and urethra of 6 weeks and 6 months old male rabbits were determined using muscle bath and autoradiographic techniques.Results: ET-1 produces significant contractile responses in smooth muscle strips from Bladder Dome, trigone, and urethra in both 6 weeks and 6 months old rabbits. Although there was no significant difference in the maximum contractile response of urethral muscle strips to ET-1 between 6 weeks and 6 months old rabbits, the maximum responses to ET-1 were higher in both Bladder Dome and trigone of 6 weeks than 6 months old rabbits. A selective ETA receptor antagonist, BQ 610, shifted the concentration response curve to ET-1 to the right without decreasing maximal contractile ...
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gene expression localization and pharmacological characterization of endothelin receptors in diabetic rat Bladder Dome
European Journal of Pharmacology, 2000Co-Authors: Motoaki Saito, Yoshihiro Wada, Kazuyoshi Ikeda, Zejing Wang, Shannon D Smith, Harris E Foster, Kazuhiko Nishi, Robert M Weiss, Jamshid LatifpourAbstract:Abstract As there are significant amounts of functional endothelin receptors in the mammalian urinary tract, we examined the effect of experimental diabetes on the expression of endothelin receptors and their mRNAs in the rat Bladder Dome. The density of endothelin receptors in the rat Bladder Dome was higher (8 and 16 weeks following the onset of diabetes) than in age-matched controls. Insulin treatment, started 8 weeks after the induction of diabetes, partially reversed the endothelin receptor alterations. The pharmacological profile of the endothelin receptors in the Bladder Dome was similar in all groups and was consistent with the predominance of the endothelin ET A receptor subtype (ET A :ET B =approximately 4:1). Autoradiographic studies demonstrated that the endothelin receptors were located in all tissue components of the Bladder, including epithelial and muscular layers. Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) data indicated that diabetes increased the expression level of gene transcripts for both endothelin receptor subtypes and that insulin treatment reversed the mRNA upregulation.
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AGE-DEPENDENT CHANGES IN PARTICULATE AND SOLUBLE GUANYLYL CYCLASE ACTIVITIES IN URINARY TRACT SMOOTH MUSCLE
Molecular and Cellular Biochemistry, 1997Co-Authors: Marcia A. Wheeler, Shinobu Dokita, Tadashi Nishimoto, Michel Pontari, Ki Whan Hong, Robert M WeissAbstract:Regional and age specific differences are observed in the sodium nitroprusside induced relaxation responses in the urinary tract. To clarify these differences, guanylyl cyclase activity is assayed in particulate and soluble fractions from the ureter, Bladder Dome, and urethra of young (11-18 days), adult (90-100 days), and old adult (2-3 years) guinea pigs. The rank order of soluble guanylyl cyclase activities is urethra = ureter > Bladder Dome with the largest decreases with aging occurring in the Bladder. Atrial natriuretic factor (10-7 M) increases particulate guanylyl cyclase activity in the three tissues at all ages tested, with the activity being highest in the ureter. ATP (0.5 mM) activates particulate guanylyl cyclase in the ureter, Bladder and urethra of old adult guinea pigs, and enhances atrial natriuretic factor induced activation of particulate guanylyl cyclase in all tissues and at all ages tested. The higher levels of soluble guanylyl cyclase activity in the urethra and ureter compared to the Bladder parallel sodium nitroprusside induced relaxation in these tissues.
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Evidence for the Presence of Regional Differences in the Subtype Specificity of Muscarinic Receptors in Rabbit Lower Urinary Tract
The Journal of Urology, 1997Co-Authors: Shinji Mutoh, Motoaki Saito, Jamshid Latifpour, Robert M WeissAbstract:ABSTRACTTo elucidate the subtype specificity of muscarinic cholinergic receptors in mediating contractile responses in the lower urinary tract, we investigated contractile and biochemical properties of muscarinic receptors in Bladder Dome, Bladder base and urethra of the rabbit. Isometric contractile response curves to increasing concentrations of carbachol were constructed in the absence and presence of various concentrations of subtype selective muscarinic antagonists. Bladder Dome, Bladder base, and urethra demonstrate different characteristics in terms of efficacy and potency with respect to carbachol-induced contractile responses. Emax values are significantly larger and ED50 values are significantly smaller in Bladder Dome and Bladder base than in urethra. Calculation of the pA2 values, the negative logarithm of the antagonist affinity constant (KB), for a series of muscarinic antagonists, i.e., atropine (nonselective), pirenzepine (M1 selective), methoctramine (M2 selective), and 4-DAMP (M1/M3 sele...
Jamshid Latifpour - One of the best experts on this subject based on the ideXlab platform.
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Developmental aspects of endothelin receptors in rabbit lower urinary tract.
Neurourology and Urodynamics, 2020Co-Authors: Motoaki Saito, Jamshid Latifpour, Robert M WeissAbstract:Since evidence of development/age-related alterations of endothelin receptors in circulation and respiration systems has been increasing, we attempted to investigate the pharmacological characterization of endothelin receptors in neonatal, premature, and mature male rabbit lower urinary tract. The biochemical properties of ET receptors were examined in the lower urinary tracts of 1-day (neonatal)-, 6-week (premature)-, and 1-year(mature)-old male rabbits with binding technique utilizing [125I]ET-1. The rank orders of the densities (Bmax values) of endothelin receptors in the Bladder Dome, Bladder base, and urethra of different aged rabbits were Bladder Dome, 1 day > 6 week vLs 1 year, Bladder base, 1 day > 6 week vLs 1 year, and urethra, 1 day > 6 week > 1 year. The pharmacological profiles of these binding sites inhibited by various kinds of endothelin receptor compounds showed similar Ki values and similar proportions of endothelin receptor subtypes in the same regions of 1-day-, 6-week-, and 1-year-old animals. Our data clearly demonstrated the presence of regional difference and development-related changes in the density and subtype specificity of endothelin receptors in the lower urinary tract of the male rabbit. Neurourol. Urodynam. 19:71–85, 2000. © 2000 Wiley-Liss, Inc.
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Age-related changes in contractile responses of rabbit lower urinary tract to endothelin.
The Journal of Urology, 2000Co-Authors: Yoshihiro Wada, Motoaki Saito, Zejing Wang, Kazuhiko Nishi, Jamshid Latifpour, Hiromi Sanematsu, Parviz Afiatpour, Robert M WeissAbstract:Purpose: As there are significant amounts of endothelin (ET) receptors in the mammalian urinary tract, we investigated the pharmacological properties and localization of ET receptors in the rabbit lower urinary tract as a function of age.Materials and Methods: The characteristics of ET receptors in Bladder Dome, trigone and urethra of 6 weeks and 6 months old male rabbits were determined using muscle bath and autoradiographic techniques.Results: ET-1 produces significant contractile responses in smooth muscle strips from Bladder Dome, trigone, and urethra in both 6 weeks and 6 months old rabbits. Although there was no significant difference in the maximum contractile response of urethral muscle strips to ET-1 between 6 weeks and 6 months old rabbits, the maximum responses to ET-1 were higher in both Bladder Dome and trigone of 6 weeks than 6 months old rabbits. A selective ETA receptor antagonist, BQ 610, shifted the concentration response curve to ET-1 to the right without decreasing maximal contractile ...
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gene expression localization and pharmacological characterization of endothelin receptors in diabetic rat Bladder Dome
European Journal of Pharmacology, 2000Co-Authors: Motoaki Saito, Yoshihiro Wada, Kazuyoshi Ikeda, Zejing Wang, Shannon D Smith, Harris E Foster, Kazuhiko Nishi, Robert M Weiss, Jamshid LatifpourAbstract:Abstract As there are significant amounts of functional endothelin receptors in the mammalian urinary tract, we examined the effect of experimental diabetes on the expression of endothelin receptors and their mRNAs in the rat Bladder Dome. The density of endothelin receptors in the rat Bladder Dome was higher (8 and 16 weeks following the onset of diabetes) than in age-matched controls. Insulin treatment, started 8 weeks after the induction of diabetes, partially reversed the endothelin receptor alterations. The pharmacological profile of the endothelin receptors in the Bladder Dome was similar in all groups and was consistent with the predominance of the endothelin ET A receptor subtype (ET A :ET B =approximately 4:1). Autoradiographic studies demonstrated that the endothelin receptors were located in all tissue components of the Bladder, including epithelial and muscular layers. Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) data indicated that diabetes increased the expression level of gene transcripts for both endothelin receptor subtypes and that insulin treatment reversed the mRNA upregulation.
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Evidence for the Presence of Regional Differences in the Subtype Specificity of Muscarinic Receptors in Rabbit Lower Urinary Tract
The Journal of Urology, 1997Co-Authors: Shinji Mutoh, Motoaki Saito, Jamshid Latifpour, Robert M WeissAbstract:ABSTRACTTo elucidate the subtype specificity of muscarinic cholinergic receptors in mediating contractile responses in the lower urinary tract, we investigated contractile and biochemical properties of muscarinic receptors in Bladder Dome, Bladder base and urethra of the rabbit. Isometric contractile response curves to increasing concentrations of carbachol were constructed in the absence and presence of various concentrations of subtype selective muscarinic antagonists. Bladder Dome, Bladder base, and urethra demonstrate different characteristics in terms of efficacy and potency with respect to carbachol-induced contractile responses. Emax values are significantly larger and ED50 values are significantly smaller in Bladder Dome and Bladder base than in urethra. Calculation of the pA2 values, the negative logarithm of the antagonist affinity constant (KB), for a series of muscarinic antagonists, i.e., atropine (nonselective), pirenzepine (M1 selective), methoctramine (M2 selective), and 4-DAMP (M1/M3 sele...
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reversibility of diabetes and diuresis induced alterations in rat Bladder Dome muscarinic receptors
Diabetes, 1994Co-Authors: Yuji Fukomoto, Robert M Weiss, Masaki Yoshida, Jamshid LatifpourAbstract:Previous studies from our laboratory demonstrated that 8 weeks of streptozocin (STZ)-induced diabetes and sucrose-fed diuresis resulted in increases in the density of muscarinic receptors in rat Bladder Dome and that early insulin treatment (started 3 days after the onset of diabetes) prevented the diabetes-induced upregulation ( J Pharmacol Exp Ther 248:81–88, 1989; Diabetes 40: 1150–1156, 1991; J Urol 147:760–763, 1992). To determine whether diabetes- and diuresis-induced alterations in muscarinic receptors in rat Bladder Dome are reversible, we administered insulin (beginning 8 weeks after the onset of diabetes) or removed sucrose from drinking water of diuretic rats (beginning 8 weeks after the onset of diuresis). Five groups of rats were maintained for 16 weeks: 1 ) STZ-induced diabetic rats (65 mg/kg intravenously); 2 ) insulin-treated diabetic rats (5–8 U/day insulin subcutaneously beginning 8 weeks after the onset of diabetes); 3 ) sucrose-fed diuretic rats (5% sucrose in drinking water throughout 16 weeks); 4 ) sucrose-removed rats (sucrose withdrawn from drinking water after 8 weeks of the sucrose-induced diuretic state); and 5) age-matched control rats. Radioligand receptor binding experiments with [ 3 H]quinuclidinyl benzilate showed an increase in the density of muscarinic receptors in Bladder Dome of diabetic and sucrose-fed rats compared with age-matched control rats. Removing the 5% sucrose from the drinking water of diuretic rats reversed the increased water intake and urine output, decreased the Bladder hypertrophy that accompanied the diuretic state, and corrected the upregulation of the muscarinic receptors. Late insulin treatment also improved (to a lesser extent than removing the sucrose) the Bladder enlargement, polydipsia, polyuria, and the muscarinic receptor upregulation in diabetic rats. Pharmacological evaluation indicated that the induction of diabetes did not affect muscarinic subtype specificity but did result in an alteration in muscarinic receptor-G protein coupling in rat Bladder Dome.
Motoaki Saito - One of the best experts on this subject based on the ideXlab platform.
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Developmental aspects of endothelin receptors in rabbit lower urinary tract.
Neurourology and Urodynamics, 2020Co-Authors: Motoaki Saito, Jamshid Latifpour, Robert M WeissAbstract:Since evidence of development/age-related alterations of endothelin receptors in circulation and respiration systems has been increasing, we attempted to investigate the pharmacological characterization of endothelin receptors in neonatal, premature, and mature male rabbit lower urinary tract. The biochemical properties of ET receptors were examined in the lower urinary tracts of 1-day (neonatal)-, 6-week (premature)-, and 1-year(mature)-old male rabbits with binding technique utilizing [125I]ET-1. The rank orders of the densities (Bmax values) of endothelin receptors in the Bladder Dome, Bladder base, and urethra of different aged rabbits were Bladder Dome, 1 day > 6 week vLs 1 year, Bladder base, 1 day > 6 week vLs 1 year, and urethra, 1 day > 6 week > 1 year. The pharmacological profiles of these binding sites inhibited by various kinds of endothelin receptor compounds showed similar Ki values and similar proportions of endothelin receptor subtypes in the same regions of 1-day-, 6-week-, and 1-year-old animals. Our data clearly demonstrated the presence of regional difference and development-related changes in the density and subtype specificity of endothelin receptors in the lower urinary tract of the male rabbit. Neurourol. Urodynam. 19:71–85, 2000. © 2000 Wiley-Liss, Inc.
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Age-related changes in contractile responses of rabbit lower urinary tract to endothelin.
The Journal of Urology, 2000Co-Authors: Yoshihiro Wada, Motoaki Saito, Zejing Wang, Kazuhiko Nishi, Jamshid Latifpour, Hiromi Sanematsu, Parviz Afiatpour, Robert M WeissAbstract:Purpose: As there are significant amounts of endothelin (ET) receptors in the mammalian urinary tract, we investigated the pharmacological properties and localization of ET receptors in the rabbit lower urinary tract as a function of age.Materials and Methods: The characteristics of ET receptors in Bladder Dome, trigone and urethra of 6 weeks and 6 months old male rabbits were determined using muscle bath and autoradiographic techniques.Results: ET-1 produces significant contractile responses in smooth muscle strips from Bladder Dome, trigone, and urethra in both 6 weeks and 6 months old rabbits. Although there was no significant difference in the maximum contractile response of urethral muscle strips to ET-1 between 6 weeks and 6 months old rabbits, the maximum responses to ET-1 were higher in both Bladder Dome and trigone of 6 weeks than 6 months old rabbits. A selective ETA receptor antagonist, BQ 610, shifted the concentration response curve to ET-1 to the right without decreasing maximal contractile ...
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gene expression localization and pharmacological characterization of endothelin receptors in diabetic rat Bladder Dome
European Journal of Pharmacology, 2000Co-Authors: Motoaki Saito, Yoshihiro Wada, Kazuyoshi Ikeda, Zejing Wang, Shannon D Smith, Harris E Foster, Kazuhiko Nishi, Robert M Weiss, Jamshid LatifpourAbstract:Abstract As there are significant amounts of functional endothelin receptors in the mammalian urinary tract, we examined the effect of experimental diabetes on the expression of endothelin receptors and their mRNAs in the rat Bladder Dome. The density of endothelin receptors in the rat Bladder Dome was higher (8 and 16 weeks following the onset of diabetes) than in age-matched controls. Insulin treatment, started 8 weeks after the induction of diabetes, partially reversed the endothelin receptor alterations. The pharmacological profile of the endothelin receptors in the Bladder Dome was similar in all groups and was consistent with the predominance of the endothelin ET A receptor subtype (ET A :ET B =approximately 4:1). Autoradiographic studies demonstrated that the endothelin receptors were located in all tissue components of the Bladder, including epithelial and muscular layers. Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) data indicated that diabetes increased the expression level of gene transcripts for both endothelin receptor subtypes and that insulin treatment reversed the mRNA upregulation.
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Direct detection of nitric oxide in rat urinary Bladder during ischemia-reperfusion
The Journal of Urology, 1999Co-Authors: Motoaki Saito, Ikuo MiyagawaAbstract:ABSTRACTPurpose: We attempted to investigate the role of nitric oxide (NO) in ischemia-reperfusion injury in the rat Bladder.Materials and Methods: Rat abdominal aorta were clamped with a small clip to induce ischemia-reperfusion injury in the rat Bladder Dome. To investigate the role of NO in ischemia-reperfusion injury, NG-nitro-L-arginine methylester (L-NAME, 30 mg./kg.) was injected intraperitoneally to measure carbachol-induced contractions of 60 minutes ischemia-30 minutes reperfusion in the rat Bladder Dome. In vivo real-time blood flow and NO release were measured in the rat Bladder with a laser Doppler flowmeter and an NO-selective electrode, respectively. Moreover, participation of NO synthase subtypes was investigated by immunohistochemical staining of Bladder sections with anti-endothelial I and anti-inducible NO synthase subtype antibodies.Result: Treatment with L-NAME (30 mg./kg., i.p.) partially prevented the reduction of Bladder strips in contraction induced by the ischemia-reperfusion. Cl...
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effect of ischemia reperfusion on contractile function of rat urinary Bladder possible role of nitric oxide
Life Sciences, 1998Co-Authors: Motoaki Saito, Kouichirou Wada, Yoshinori Kamisaki, Ikuo MiyagawaAbstract:Because there are increasing evidences that nitric oxide (NO) plays important roles in ischemia-reperfusion injury in several systems, we investigated the role of NO in ischemiareperfusion injury of the rat urinary Bladder. Rat abdominal aorta was clamped with a small clip to induce ischemia-reperfusion injury in the rat Bladder Dome. In functional studies, contractile responses to carbachol were cumulatively measured after the urinary Bladder was treated with various duration (0, 30, 60, and 90 min) of ischemia. The injury of rat Bladder functioning was dependent on ischemic periods. Significant decreases in the Emax (maximum contractile response) values were observed in the Bladder subjected to 60 or 90 min ischemia. Furthermore, the subsequent 30 min reperfusion caused additional damages of the contractile response in Bladder muscles. To investigate the role of NO in the ischemia (30 min)-reperfusion (30 min) injury, NG-nitro-L-arginine methylester (L-NAME) was injected intraperitoneally 30 min before the ischemia. Treatment of L-NAME (30 and 100 mgkg) partly but significantly prevented the reduction contractile responses to carbachol of the rat Bladder Dome. In histological studies, the ischemia-reperfusion caused infiltration of leukocytes and rupture of microcirculation in the regions of submucosa and smooth muscle without a corresponding sloughing of mucosal cells. The histological damages were also prevented by treatment with L-NAME. Therefore, these data suggested that ischemia-reperfusion of the urinary Bladder may result in dysfunction of the contractile response to autonomic nervous system and that nitric oxide may act as a cell/tissue damaging agent in ischemia-reperfusion injury.
Masaki Yoshida - One of the best experts on this subject based on the ideXlab platform.
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the β3 adrenoceptor mediates the inhibitory effects of β adrenoceptor agonists via the urothelium in pig Bladder Dome
Neurourology and Urodynamics, 2010Co-Authors: Koichi Masunaga, Masaki Yoshida, Christopher R Chapple, Neil G Mckay, Donna J SellersAbstract:Aims: Relaxation of detrusor muscle via beta-adrenoceptors may contribute to urine storage during Bladder filling. Thus there is increasing interest in beta-adrenoceptor agonists as a potential treatment for detrusor overactivity. The role of the urothelium in Bladder responses to beta-adrenoceptor agonists is not yet clear, although we have shown that these agonists have a greater inhibitory effect on detrusor contraction when the urothelium is intact. The aim was to determine which beta-adrenoceptor subtype is involved in this effect. Methods: Paired strips of pig Bladder Dome mucosa-intact and mucosa-denuded, were mounted in tissue baths. Relaxation responses were obtained to beta-adrenoceptor agonists (isoprenaline, dobutamine, salbutamol or BRL37344) in carbachol pre-contracted tissues. Inhibitory effects were studied by obtaining concentration-response curves (CRCs) to carbachol in the presence and absence of beta-adrenoceptor agonists. The inhibitory effects of isoprenaline were also studied following incubation with beta-adrenoceptor antagonists (propranolol, CGP20712, ICI-118, 551 or SR 59230A; non selected, beta(1), beta(2) and beta(3) selective respectively). Results: isoprenaline, dobutamine, salbutamol and BRL37344 all relaxed carbachol pre-contracted tissues and responses were similar in intact and denuded strips. In inhibition experiments, padrenoceptor agonists caused rightward shifts of carbachol CRCs. In intact strips the shift was greater with isoprenaline and BRL37344, but not with dobutamine or salbutamol. This increased shift was still observed in tissues pre-incubated with propranolo, CGP20712 and ICI-118, 551, but not with SR 59230A. Conclusions: beta(3)-adrenoceptors are involved in mediating inhibitory effects of beta-adrenoceptor agonists on detrusor contractions via the urothelium in pig Bladder Dome.
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reversibility of diabetes and diuresis induced alterations in rat Bladder Dome muscarinic receptors
Diabetes, 1994Co-Authors: Yuji Fukomoto, Robert M Weiss, Masaki Yoshida, Jamshid LatifpourAbstract:Previous studies from our laboratory demonstrated that 8 weeks of streptozocin (STZ)-induced diabetes and sucrose-fed diuresis resulted in increases in the density of muscarinic receptors in rat Bladder Dome and that early insulin treatment (started 3 days after the onset of diabetes) prevented the diabetes-induced upregulation ( J Pharmacol Exp Ther 248:81–88, 1989; Diabetes 40: 1150–1156, 1991; J Urol 147:760–763, 1992). To determine whether diabetes- and diuresis-induced alterations in muscarinic receptors in rat Bladder Dome are reversible, we administered insulin (beginning 8 weeks after the onset of diabetes) or removed sucrose from drinking water of diuretic rats (beginning 8 weeks after the onset of diuresis). Five groups of rats were maintained for 16 weeks: 1 ) STZ-induced diabetic rats (65 mg/kg intravenously); 2 ) insulin-treated diabetic rats (5–8 U/day insulin subcutaneously beginning 8 weeks after the onset of diabetes); 3 ) sucrose-fed diuretic rats (5% sucrose in drinking water throughout 16 weeks); 4 ) sucrose-removed rats (sucrose withdrawn from drinking water after 8 weeks of the sucrose-induced diuretic state); and 5) age-matched control rats. Radioligand receptor binding experiments with [ 3 H]quinuclidinyl benzilate showed an increase in the density of muscarinic receptors in Bladder Dome of diabetic and sucrose-fed rats compared with age-matched control rats. Removing the 5% sucrose from the drinking water of diuretic rats reversed the increased water intake and urine output, decreased the Bladder hypertrophy that accompanied the diuretic state, and corrected the upregulation of the muscarinic receptors. Late insulin treatment also improved (to a lesser extent than removing the sucrose) the Bladder enlargement, polydipsia, polyuria, and the muscarinic receptor upregulation in diabetic rats. Pharmacological evaluation indicated that the induction of diabetes did not affect muscarinic subtype specificity but did result in an alteration in muscarinic receptor-G protein coupling in rat Bladder Dome.
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Age-related changes in Ca2+ channel antagonist receptors in rabbit lower urinary tract.
European Journal of Pharmacology, 1993Co-Authors: Masaki Yoshida, Jamshid Latifpour, Robert M WeissAbstract:(+)-[3H]PN 200-110 and [3H]nitrendipine binding sites were studied in 1 day, 6 week, 6 month and 4.5–5 year rabbit urethra, Bladder base and Bladder Dome. In all age groups, the density of these Ca2+ channel antagonist binding sites was significantly greater in the urethra than in the Bladder base or Bladder Dome, except that the density of [3H]nitrendipine binding sites in the 1 day rabbit was similar in all three regions. In the urethra the maximum number of binding sites for (+)-[3H]PN 200-110 was twice that for [3H]nitrendipine. In the Bladder Dome both Ca2+ channel antagonists labelled a similar number of binding sites. For both ligands, the Bmax values for the Ca2+ channel antagonists in the urethra increased from 1 day to 6 weeks and then decreased. In the Bladder base and Dome, however, the receptor density decreased gradually or was unchanged with aging. The pharmacological profiles of these binding sites in 1 day and 6 month urethra and Bladder Dome showed K1 values with the following rank order: nitrendipine < niguldipine < BAY K 8644. These data demonstrate the presence of regional- and age-dependent changes in the density of Ca2+ channel antagonist binding sites in the lower urinary tract of the rabbit.
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Evidence for the presence of regional differences in the calcium antagonist receptors in lower urinary tract smooth muscle
Naunyn-Schmiedeberg's Archives of Pharmacology, 1992Co-Authors: Jamshid Latifpour, Masaki Yoshida, Robert M WeissAbstract:(+)-[^3HPN 200-110 (a dihydropyridine calcium channel antagonist) was utilized to characterize calcium channel binding sites in rabbit Bladder Dome, Bladder base, and urethra. Specific binding of (+)-[^3H]PN 200-110 to membrane particulates was saturable, reversible, linear to protein concentration, and of high affinity. The density of (+)-[^3H]PN 200-110 binding sites (B_max values in fmol/mg of protein) and the affinity constants for (+)-[^3H]PN 200-110 (K_D value in pM) in urethra, Bladder Dome and Bladder base were 64.1 ± 7.8 and 179±31; 21.9±3.0 and 213±36; and 18.8±4.2 and 140±28, respectively. Agonists and antagonists inhibited (+)-[^3H]PN 200-110 binding with Ki values in the following rank order: nitrendipine < nifedipine < niguldipine ≪ Bay K 8644 ≪ verapamil. Although carbachol-induced contractile responses were 20–30 times smaller in muscle strips from urethra than from Bladder base or Bladder Dome, KCl-induced contractions were only 3–4 times smaller in urethra than in Bladder tissues. Nifedipine inhibited carbachol-induced contractions in urethra, Bladder Dome, and Bladder base by 76%, 64%, and 60%, respectively, and completely inhibited KCl-induced contractions in all three tissues. IC_50 values for nifedipine inhibition of both carbachol- and KCl-induced contractions were significantly smaller in urethra than in Bladder base or Bladder Dome. Nitrendipine, niguldipine and verapamil inhibited urethral contractions induced by carbachol and KCl to the same degree as did nifedipine. The IC_50 values, obtaines from functional studies, for calcium channel antagonists were in good agreement with Ki values obtained from binding studies. BAY K 8644, a calcium channel agonist, increased both KCl- and carbachol-induced contractions and potentiated CaCl_2-induced contractions in K+-depolarizing media in urethra but not in Bladder Dome or Bladder base. Our data indicate that the density of (+)-[^3H]PN 200-110 binding sites is higher in the urethra than in the Bladder Dome or Bladder base and that the urethra is functionally more sensitive to dihydropyridine agonists and antagonists than is either the Bladder Dome or Bladder base.
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Effect of insulin and dietary myoinositol on muscarinic receptor alterations in diabetic rat Bladder.
The Journal of Urology, 1992Co-Authors: Jamshid Latifpour, Masaki Yoshida, Angelo Gousse, Robert M WeissAbstract:Abstract Previous studies from our laboratory demonstrated that there is an up-regulation of muscarinic receptor density in the Bladder Dome of the 8-wks diabetic rat compared to control. To determine whether the changes observed in receptor density can be corrected by insulin or dietary myoinositol, five groups of rats were maintained for eight weeks: control (C), diabetic (D), diabetic insulin-treated (DI), diabetic myoinositol-treated (DMI), and control myoinositol-treated (CMI). Diabetes was induced by i.v. injection of 65 mg./kg. of streptozotocin. D and DMI animals were smaller, had higher serum glucose and lower serum insulin levels, higher water intakes and urine outputs, and larger Bladder Domes than the other groups. The density of the muscarinic receptors measured by radioligand receptor binding assays using [ 3 H]quinuclidinyl benzilate were (in fmol./mg. protein): C, 88 ± 13; D, 176 ± 19; DI, 94 ± 5; DMI, 158 ± 8; CMI, 112 ± 10. These data indicate that insulin, but not myoinositol treatment normalized diabetes induced abnormalities observed in the general features of streptozotocin-injected rats and prevented the diabetic-induced upregulation of Bladder Dome muscarinic receptors.
Francois Giuliano - One of the best experts on this subject based on the ideXlab platform.
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signalling pathways involved in sildenafil induced relaxation of human Bladder Dome smooth muscle
British Journal of Pharmacology, 2010Co-Authors: Stephanie Oger, D Behrroussel, Diane Gorny, Thierry Lebret, Pierre Validire, Xavier Cathelineau, Laurent Alexandre, Francois GiulianoAbstract:Background and purpose: The mechanism(s) of action responsible for the beneficial effects of phosphodiesterase 5 (PDE5) inhibitors including sildenafil on lower urinary tract symptoms suggestive of benign prostate hyperplasia are unclear. In particular, the role of the NO-cGMP signalling pathway in regulating human Bladder Dome smooth muscle relaxation is questionable. Thus, we assessed the ability of a PDE5 inhibitor, sildenafil, to relax such tissue, and identified the signalling pathways involved in this relaxation. Experimental approach: Human Bladder samples were obtained from 20 patients with no overactive Bladder undergoing cystectomy for Bladder cancer. Detrusor strips were mounted isometrically in Krebs–HEPES solution. Concentration–response curves for sildenafil (10 nM–30 µM) were generated in the presence of various inhibitors on carbachol-induced pre-contraction. Key results: Sildenafil relaxed carbachol-pre-contracted human detrusor strips, starting at 3 µM. This effect was not modified by NO donors, S-nitroso-N-acetylpenicillamine (10 µM) or sodium nitroprusside (300 nM), but was significantly inhibited by inhibition of guanylate cyclase (with ODQ, 10 µM) or adenylyl cyclase (with MDL-12,330A, 10 µM), by the ATP-sensitive potassium channel inhibitor, glibenclamide (10 µM), or inhibition of the large (with iberiotoxin, 30 nM) or small (with apamin, 100 nM) conductance calcium-activated potassium channels. Conclusions and implications: Sildenafil-induced relaxation of human detrusor smooth muscle involved cGMP-, cAMP- and K+ channel-dependent signalling pathways, with a minor contribution from NO. The effect of this sildenafil-induced relaxation on the clinical benefit of PDE5 inhibitors on urinary storage symptoms in men deserves further investigation.