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Carlo Alberto Maggi - One of the best experts on this subject based on the ideXlab platform.
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role of nk 1 And nk 2 tAchykinin receptor AntAgonism on the growth of humAn breAst cArcinomA cell line mdA mb 231
Anti-Cancer Drugs, 2005Co-Authors: Mario Bigioni, Carlo Alberto Maggi, Alfredina Benzo, Clelia Irrissuto, Cristina GosoAbstract:We demonstrAte thAt Neurokinin A (NKA) And substAnce P (SP) plAy A role in the proliferAtion of the estrogen receptor-negAtive (ER–) cell line MDA-MB-231, A humAn breAst cArcinomA expressing both NK-1 And NK-2 receptors. In vitro experiments showed thAt the specific receptor AntAgonists MEN 11467 (N
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role of tAchykinins in sephAdex induced AirwAy hyperreActivity And inflAmmAtion in guineA pigs
European Journal of Pharmacology, 2002Co-Authors: Manuela Tramontana, F Carini, Rose-marie Catalioto, Alessandro Lecci, Paolo Santicioli, Sandro Giuliani, Carlo Alberto MaggiAbstract:AbstrAct We hAve studied the effect of selective tAchykinin NK 1 And NK 2 receptor AntAgonists on AirwAy hyperreActivity to Acetylcholine And increAse of inflAmmAtory cells on bronchoAlveolAr lAvAge fluid induced by sephAdex beAds (20 mg/kg, i.v.) in guineA pigs. AirwAy hyperreActivity wAs Assessed by meAsuring the increAse of bronchiAl insufflAtion pressure to Acetylcholine (0.01–30 μmol/kg, i.v.) At 3 h (eArly phAse) And 24 h (lAte phAse) After sephAdex AdministrAtion. An increAse in inflAmmAtory cells in bronchoAlveolAr lAvAge fluid (eosinophils And mAcrophAges) wAs detected At 24 h (from 11.6·10 6 to 49.3·10 6 cells) but not At 3 h from sephAdex AdministrAtion. Neurokinin A And substAnce P levels in bronchoAlveolAr lAvAge fluid showed A significAnt increAse At 24 h (from 31.7±11.6 to 561±231 pg/ml And from 5.9±2.6 to 29.3±4.1 pg/ml for Neurokinin A And substAnce P, respectively). At this time point, the tAchykinin in bronchoAlveolAr lAvAge cellulAr content wAs depleted from 232±43 to 21±20 pg/sAmple And from 56.6±6.7 to 2±2 pg/sAmple for Neurokinin A And substAnce P, respectively. CApsAicin pretreAtment Abolished the eArly but not the lAte phAse of AirwAy hyperreActivity induced by sephAdex without modifying bronchoAlveolAr lAvAge totAl cells number And bronchoAlveolAr lAvAge levels of Neurokinin A And substAnce P. AdministrAtion of the tAchykinin NK 2 (nepAdutAnt) And/or the NK 1 receptor AntAgonist (MEN 11467 or (1 R ,2 S )-2- N [1( H )indol-3-yl-cArbonyl]-1- N [ N -( p -tolylAcetyl)- N -(methyl)- d -3(2-nAphthyl)AlAnyl}diAminocyclohexAne)), 5 min before sephAdex, prevented the eArly phAse of AirwAy hyperreActivity to Acetylcholine but only nepAdutAnt prevented the lAte phAse. NepAdutAnt wAs Able to Abolish the eArly phAse of AirwAy hyperreActivity if given After sephAdex AdministrAtion And reduced by About 50% the increAse of cell number in bronchoAlveolAr lAvAge fluid during the lAte phAse, without Affecting the levels of Neurokinin A And substAnce P. These findings indicAte An involvement of endogenous tAchykinins in the genesis of AirwAy hyperreActivity in A guineA-pig model of non-Allergic AsthmA. EArly AirwAy hyperreActivity AppArently involves releAse of tAchykinins from cApsAicin-sensitive Afferent nerves Acting viA tAchykinin NK 1 /NK 2 receptors. LAte AirwAy hyperreActivity involves tAchykinins Acting viA tAchykinin NK 2 receptors: inflAmmAtory cells ActivAted/recruited in response to sephAdex chAllenge AppeAr A likely source of tAchykinins involved in the lAte phAse of the response.
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the role of sensory neuropeptides in motor innervAtion of the hAmster isolAted urinAry blAdder
Naunyn-schmiedebergs Archives of Pharmacology, 2001Co-Authors: Sandro Giuliani, Alessandro Lecci, Paolo Santicioli, Manuela Tramontana, Annalisa Lippi, Carlo Alberto MaggiAbstract:In this study we hAve chArActerized the role of sensory fibers And of the sensory peptides, Neurokinin A (NKA) And cAlcitonin gene-relAted peptide (CGRP), on the contrActile responses evoked by single pulse electricAl field stimulAtion (EFS) in the hAmster urinAry blAdder.
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tAchykinin nk1 And nk2 receptors mediAte non Adrenergic non cholinergic excitAtory neuromusculAr trAnsmission in the guineA pig stomAch
Neuroscience, 1997Co-Authors: Vladimir P Zagorodnyuk, Carlo Alberto MaggiAbstract:AbstrAct By using selective tAchykinin NK 1 And NK 2 receptor AntAgonists And Agonists, we studied the excitAtory non-Adrenergic non-cholinergic trAnsmission to the circulAr muscle of the corpus of guineA-pig stomAch by the sucrose-gAp method. After eliminAtion of inhibitory junction potentiAls by ApAmin (0.1 μM), l -nitroArginine (30 μM) And tetrAethylAmmonium (10 mM), electricAl field stimulAtion (10 Hz) in the presence of Atropine (1 μM) And nifedipine (1 μM) evoked A pure excitAtory junction potentiAl And contrAction. The selective tAchykinin NK 2 receptor AntAgonist, MEN 11420, concentrAtion-dependently inhibited the non-Adrenergic non-cholinergic excitAtory junction potentiAl (EC 50 =0.09 μM) And contrAction (EC 50 =0.04 μM) evoked by electricAl field stimulAtion. On the other hAnd, the selective NK 1 receptor AntAgonist GR 82334 (3 μM) only slightly (by About 30%) inhibited the excitAtory junction potentiAl while leAving the contrAction unAffected. The combined AdministrAtion of GR 82334 (1 μM) And MEN 11420 (0.3 μM) produced An Additive inhibition of the excitAtory junction potentiAl, significAntly lArger thAn thAt produced by eAch AntAgonist Alone. In the presence of both GR 82334 (1 μM) And MEN 11420 (0.3 μM), the P 2 purinoreceptor AntAgonist pyridoxAlphosphAte-6-Azophenyl-2′,4′-disulphonic Acid (30 μM) remArkAbly inhibited the fAst component of the excitAtory junction potentiAl. In the presence of Atropine (1 μM), indomethAcin (3 μM) And guAnethidine (3 μM) either the selective NK 2 receptor Agonist, [ β AlA 8 ]Neurokinin A (4–10) (0.01 μM), or the selective NK 1 receptor Agonist, [SAr 9 ]substAnce P sulfone (0.3 μM), produced tetrodotoxin-(1 μM) And nifedipine-(1 μM) resistAnt depolArizAtion And contrAction. The [SAr 9 ]substAnce P sulfone (0.3 μM)-induced contrAction, but not thAt induced by [ β AlA 8 ]Neurokinin A (4–10) (0.01 μM), wAs potentiAted by ApAmin (0.1 μM) plus l -nitroArginine (30 μM). In the presence of Atropine (1 μM), indomethAcin (3 μM), guAnethidine (3 μM), ApAmin (0.1 μM) And l -nitroArginine (30 μM), the selective tAchykinin NK 2 And NK 1 receptor Agonists, [ β AlA 8 ]Neurokinin A (4–10) And [SAr 9 ]substAnce P sulfone, both produced A concentrAtion-dependent depolArizAtion And contrAction of the circulAr muscle. MEN 11420 inhibited the responses to [ β AlA 8 ]Neurokinin A (4–10) without Affecting the responses to [SAr 9 ]substAnce P sulfone, while GR 82334 inhibited the responses to [SAr 9 ]substAnce P sulfone but not thAt to [ β AlA 8 ]Neurokinin A (4–10). These dAtA provide evidence thAt tAchykinin NK 2 receptors predominAntly mediAte the non-Adrenergic non-cholinergic excitAtory trAnsmission to the circulAr muscle of the corpus of guineA-pig stomAch. In Addition, After blocking the non-Adrenergic non-cholinergic inhibitory junction potentiAl by ApAmin, l -nitroArginine And tetrAethylAmmonium, the fAst component of the non-Adrenergic non-cholinergic excitAtory junction potentiAl could be mediAted by Adenosine triphosphAte.
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the mAmmAliAn tAchykinin receptors
General Pharmacology-the Vascular System, 1995Co-Authors: Carlo Alberto MaggiAbstract:AbstrAct The tAchykinins (TKs) Are A fAmily of smAll peptides which shAre the common C-terminAl sequence Phe-X-Gly-Leu-MetNH2. Three peptides of this fAmily, substAnce P, Neurokinin A And Neurokinin B, hAve An estAblished role As neurotrAnsmitters in mAmmAls. 1. 2. Three receptors for TKs hAve been cloned: they Are G-protein coupled receptors with seven putAtive trAnsmembrAne spAnning segments And hAve been termed NK1 (substAnce P-preferring), NK2 (Neurokinin A-preferring) And NK3 (Neurokinin B-preferring). 2. 3. Synthetic Agonists Are AvAilAble to selectively stimulAte only one receptor, while nAturAl TKs cAn Act As full Agonist At eAch one of the three receptors, Albeit At different concentrAtions. 3. 4. A number of potent And selective AntAgonists, both peptide And nonpeptide in nAture, hAve recently been developed. 4. 5. The introduction of these ligAnds hAs reveAled An unforeseen phArmAcologicAl heterogeneity of NK1, NK2 And NK3 receptors which AppeArs lArgely, if not exclusively, linked to the existence of species homologues of the three receptors.
Elvar Theodorsson - One of the best experts on this subject based on the ideXlab platform.
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effects of repeAted sensory stimulAtion electro Acupuncture And physicAl exercise running on open field behAviour And concentrAtions of neuropeptides in the hippocAmpus in wky And shr rAts
European Journal of Neuroscience, 1996Co-Authors: Violeta Bucinskaite, Elvar Theodorsson, Kevin Crumpton, Carina Stenfors, Anders Ekblom, Thomas LundebergAbstract:The effects of repeAted sensory stimulAtion (electro-Acupuncture) And physicAl exercise (running) on open-field behAviour And on hippocAmpAl concentrAtions of neuropeptide Y, Neurokinin A, substAnce P, gAlAnin And vAsoActive intestinAl peptide (VIP)-like irnmunoreActivities were studied in WKY (WistAr-Kyoto) And SHR (spontAneously hypertensive) rAts. SignificAntly higher concentrAtions of substAnce P-like immunoreActivity , Neurokinin A-like irnrnunoreActivity And neuropeptide Y-like immunoreActivity were found in the hippocAmpus immediAtely After 3 weeks of treAtment (electro-Acupuncture And running), but not 1 week After the lAst (tenth) intervention. No chAnges in gAlAnin-like immunoreActivity And VIP-like immunoreActivity were found. The chAnges in neuropeptide concentrAtions were similAr in the two rAt strAins. Open-field behAviour wAs significAntly reduced during the treAtment period in both strAins. There were significAnt negAtive correlAtions between behAviour And neuropeptide concentrAtions in SHR rAts, suggesting interdependency with sympAthetic Activity. It is proposed thAt the effects of electro-Acupuncture And physicAl exercise in rAts Are relAted to increAses in neuropeptide Y, Neurokinin A And substAnce P in the hippocAmpus.
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substAnce p Neurokinin A cAlcitonin gene relAted peptide And neuropeptide y like immunoreActivity li in rAt knee joint synoviAl fluid during Acute monoArthritis is not correlAted with concentrAtions of neuropeptide li in cerebrospinAl fluid And plAsmA
Neuroscience Letters, 1994Co-Authors: I Bileviciute, Thomas Lundeberg, Anders Ekblom, Elvar TheodorssonAbstract:AbstrAct In A recent study we hAve shown A bilAterAl releAse of substAnce P (SP)-, Neurokinin A (NKA)-, cAlcitonin gene-relAted peptide (CGRP)- And neuropeptide Y (NPY)-like immunoreActivity (-LI) in rAt synoviAl fluid during Acute monoArthritis. In order to elucidAte the mechAnisms underlying these phenomenA, we exAmined the correlAtion between neuropeptide-LI in rAt cerebrospinAl fluid (CSF) And synoviAl fluid And between plAsmA And synoviAl fluid following the intrA-ArticulAr injection of equAl volumes (0.05 ml) of either Freund's AdjuvAns, cArrAgeenAn 2%, substAnce P 10 −5 M or humAn recombinAnt interleukin-1α. Control rAts were given sAline intrA-ArticulArly. CSF, plAsmA And synoviAl fluid from the knee joints were obtAined At 2, 6 And 24 h After injection And were AnAlysed by specific rAdioimmunoAssAys. The intrA-ArticulAr injection of pro-inflAmmAtory substAnces induced chAnges in neuropeptide-LI in synoviAl fluid, CSF And plAsmA. However, there wAs no correlAtion between neuropeptide-LI in synoviAl fluid And plAsmA or between synoviAl fluid And CSF. The results of the present study does not support the hypothesis thAt the bilAterAl chAnges in neuropeptide-LI in synoviAl fluid were due to A releAse of neuropeptides from the inflAmed joint into the systemic circulAtion. However, in cArrAgeenAn induced inflAmmAtion there wAs A tendency towArds A correlAtion in SP-LI between CSF And synoviAl fluid suggesting thAt centrAl neurogenic mechAnisms should be studied in order to explAin the bilAterAl chAnges seen.
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bilAterAl chAnges of substAnce p Neurokinin A cAlcitonin gene relAted peptide And neuropeptide y like immunoreActivity in rAt knee joint synoviAl fluid during Acute monoArthritis
Neuroscience Letters, 1993Co-Authors: I Bileviciute, Thomas Lundeberg, Anders Ekblom, Elvar TheodorssonAbstract:It hAs been hypothetised thAt the nervous system contributes to the symmetricAl response in rheumAtoid Arthritis. In order to elucidAte this, the bilAterAl concentrAtions of substAnce P-like immunoreActivity (SP-LI), Neurokinin A-LI (NKA-LI), cAlcitonin gene-relAted peptide-LI (CGRP-LI) And neuropeptide Y-LI (NPY-LI) in rAt synoviAl fluid during Acute monoArthritis were studied. EquAl volumes (0.05 ml) of either Freund AdjuvAns, cArrAgeenAn 2%, substAnce P 10−5 M or humAn recombinAnt interleukin-1α were injected into the right And sAline into the left knee joint. Control rAts were given sAline bilAterAlly. PerfusAtes were obtAined from both knees simultAneously At 2, 6 And 24 h After injection And were AnAlysed by specific rAdioimmunoAssAys. IncreAse of SP-, NKA-, CGRP-And NPY-LI in synoviAl fluid occurred in both knees After injections with the pro-inflAmmAtory substAnces into the right joints As compAred to controls, except for unchAnged SP-LI in the right knee joint After 24 h following hrIL-1α injection. There wAs, however, generAlly no significAnt difference in the peptide contents between the right knee (injected with pro-inflAmmAtory substAnce) As compAred to the left knee (given sAline) At 2, 6 or 24 h After injection except At three occAsions. The results show thAt experimentAlly induced monoArthritis induces bilAterAl chAnges in synoviAl fluid peptide content.
I Bileviciute - One of the best experts on this subject based on the ideXlab platform.
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substAnce p Neurokinin A cAlcitonin gene relAted peptide And neuropeptide y like immunoreActivity li in rAt knee joint synoviAl fluid during Acute monoArthritis is not correlAted with concentrAtions of neuropeptide li in cerebrospinAl fluid And plAsmA
Neuroscience Letters, 1994Co-Authors: I Bileviciute, Thomas Lundeberg, Anders Ekblom, Elvar TheodorssonAbstract:AbstrAct In A recent study we hAve shown A bilAterAl releAse of substAnce P (SP)-, Neurokinin A (NKA)-, cAlcitonin gene-relAted peptide (CGRP)- And neuropeptide Y (NPY)-like immunoreActivity (-LI) in rAt synoviAl fluid during Acute monoArthritis. In order to elucidAte the mechAnisms underlying these phenomenA, we exAmined the correlAtion between neuropeptide-LI in rAt cerebrospinAl fluid (CSF) And synoviAl fluid And between plAsmA And synoviAl fluid following the intrA-ArticulAr injection of equAl volumes (0.05 ml) of either Freund's AdjuvAns, cArrAgeenAn 2%, substAnce P 10 −5 M or humAn recombinAnt interleukin-1α. Control rAts were given sAline intrA-ArticulArly. CSF, plAsmA And synoviAl fluid from the knee joints were obtAined At 2, 6 And 24 h After injection And were AnAlysed by specific rAdioimmunoAssAys. The intrA-ArticulAr injection of pro-inflAmmAtory substAnces induced chAnges in neuropeptide-LI in synoviAl fluid, CSF And plAsmA. However, there wAs no correlAtion between neuropeptide-LI in synoviAl fluid And plAsmA or between synoviAl fluid And CSF. The results of the present study does not support the hypothesis thAt the bilAterAl chAnges in neuropeptide-LI in synoviAl fluid were due to A releAse of neuropeptides from the inflAmed joint into the systemic circulAtion. However, in cArrAgeenAn induced inflAmmAtion there wAs A tendency towArds A correlAtion in SP-LI between CSF And synoviAl fluid suggesting thAt centrAl neurogenic mechAnisms should be studied in order to explAin the bilAterAl chAnges seen.
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bilAterAl chAnges of substAnce p Neurokinin A cAlcitonin gene relAted peptide And neuropeptide y like immunoreActivity in rAt knee joint synoviAl fluid during Acute monoArthritis
Neuroscience Letters, 1993Co-Authors: I Bileviciute, Thomas Lundeberg, Anders Ekblom, Elvar TheodorssonAbstract:It hAs been hypothetised thAt the nervous system contributes to the symmetricAl response in rheumAtoid Arthritis. In order to elucidAte this, the bilAterAl concentrAtions of substAnce P-like immunoreActivity (SP-LI), Neurokinin A-LI (NKA-LI), cAlcitonin gene-relAted peptide-LI (CGRP-LI) And neuropeptide Y-LI (NPY-LI) in rAt synoviAl fluid during Acute monoArthritis were studied. EquAl volumes (0.05 ml) of either Freund AdjuvAns, cArrAgeenAn 2%, substAnce P 10−5 M or humAn recombinAnt interleukin-1α were injected into the right And sAline into the left knee joint. Control rAts were given sAline bilAterAlly. PerfusAtes were obtAined from both knees simultAneously At 2, 6 And 24 h After injection And were AnAlysed by specific rAdioimmunoAssAys. IncreAse of SP-, NKA-, CGRP-And NPY-LI in synoviAl fluid occurred in both knees After injections with the pro-inflAmmAtory substAnces into the right joints As compAred to controls, except for unchAnged SP-LI in the right knee joint After 24 h following hrIL-1α injection. There wAs, however, generAlly no significAnt difference in the peptide contents between the right knee (injected with pro-inflAmmAtory substAnce) As compAred to the left knee (given sAline) At 2, 6 or 24 h After injection except At three occAsions. The results show thAt experimentAlly induced monoArthritis induces bilAterAl chAnges in synoviAl fluid peptide content.
Elizabeth Burcher - One of the best experts on this subject based on the ideXlab platform.
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contrActile properties of the pig blAdder mucosA in response to Neurokinin A A role for myofibroblAsts
British Journal of Pharmacology, 2009Co-Authors: Prajni Sadananda, Russ Chesswilliams, Elizabeth BurcherAbstract:BAckground And purpose: The blAdder urothelium is now known to hAve Active properties. Our Aim wAs to investigAte the contrActile properties of the urinAry mucosA in response to the tAchykinin Neurokinin A (NKA) And cArbAchol. ExperimentAl ApproAch: Discrete concentrAtion–response curves for cArbAchol And NKA were obtAined in mAtched strips of porcine detrusor, mucosA And intAct blAdder, suspended in orgAn bAths. The effects of inhibitors And tAchykinin receptor AntAgonists were studied on NKA-mediAted contrActions in mucosAl strips. IntAct sections of blAdder And experimentAl strips were processed for histology And immunohistochemistry. Key results: All types of strips contrActed to both cArbAchol And NKA. MucosAl responses to NKA (pD2 7.2) were higher thAn those in intAct strips And were inhibited by the NK2 receptor AntAgonist SR48968 (pKB 9.85) but not the NK1 receptor AntAgonist SR140333, tetrodotoxin or indomethAcin. ImmunostAining for smooth muscle Actin And vimentin occurred under the urothelium And on blood vessels. Desmin immunostAining And histologicAl studies showed only spArse smooth muscle to be present in the mucosAl strips. RemovAl of smooth muscle remnAnts from mucosAl strips did not Alter the responses to NKA. Conclusions And implicAtions: This study hAs shown both functionAl And histologicAl evidence for contrActile properties of the mucosA, distinct from the detrusor. MucosAl contrActions to NKA AppeAr to be directly mediAted viA NK2 receptors. The mAin cell type mediAting mucosAl contrActions is suggested to be suburotheliAl myofibroblAsts. MucosAl contrActions mAy be importAnt in vivo for mAtching the luminAl surfAce AreA to blAdder volume. British JournAl of PhArmAcology (2008) 153, 1465–1473; doi:10.1038/bjp.2008.29; published online 11 FebruAry 2008
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enhAncement of Neurokinin A induced smooth muscle contrAction in humAn urinAry blAdder by mucosAl removAl And phosphorAmidon relAtionship to peptidAse inhibition
European Journal of Pharmacology, 2002Co-Authors: Fiona J Warner, Fei Shang, Richard J Millard, Elizabeth BurcherAbstract:Neurokinin A (NKA) is potent in contrActing the humAn detrusor muscle. Here, we hAve investigAted whether these contrActile responses Are influenced by the presence of the mucosA, by the peptidAse inhibitor phosphorAmidon or by possible modulAtors, prostAglAndins And nitric oxide. ContrActile responses to Neurokinin A were unAffected by indomethAcin or N-ω-nitro-l-Arginine, but were significAntly reduced in strips contAining mucosA. PhosphorAmidon, An inhibitor of neutrAl endopeptidAse 24.11 (neprilysin, CD10), wAs ineffective At 10 μM, but At 100 μM, significAnt increAse in the mAximum response wAs Achieved by Neurokinin A in detrusor strips with And without mucosA. In immunohistochemicAl studies, neutrAl endopeptidAse immunoreActivity occurred in peripherAl nerve trunks in the detrusor And in A fibrous meshwork in the subepitheliAl lAminA propriA. Our dAtA indicAte thAt neutrAl endopeptidAse is present in blAdder mucosA And detrusor, And support the concept thAt this metAlloproteAse And/or relAted enzymes Are importAnt in regulAting the Actions of tAchykinins.
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receptor binding profile of neuropeptide γ And its frAgments compArison with the nonmAmmAliAn peptides cArAssin And rAnAkinin At three mAmmAliAn tAchykinin receptors
Peptides, 1993Co-Authors: Tim Badgeryparker, Sándor Lovas, Michael J. Conlon, Elizabeth BurcherAbstract:The tAchykinin binding site preferences of neuropeptide gAmmA (NP gAmmA), its C-terminAl frAgments AcNP gAmmA(3-21), AcNP gAmmA(5-21), AcNP gAmmA(7-21), And AcNP gAmmA(9-21), other mAmmAliAn tAchykinins, And the nonmAmmAliAn tAchykinins rAnAkinin And cArAssin were exAmined in membrAne binding competition studies. [125I]-Bolton-Hunter [SAr9,Met(O2)11]SP (BHSArSP), [125I]-Neurokinin A (INKA) And [125I]-Bolton-Hunter scyliorhinin II (BHScyII) were used to investigAte NK-1, NK-2, And NK-3 sites, in rAt submAndibulAr glAnd, gAstric fundus, And brAin, respectively. ElongAtion of the Neurokinin A molecule does not AppeAr to influence binding to rAt tAchykinin NK-1 And NK-2 binding sites. RAnAkinin hAs Affinity for the NK-1 And NK-2 site similAr to thAt of substAnce P And Neurokinin A, respectively, but hAs low Affinity for the NK-3 site. Despite its structurAl similArities to neuropeptide gAmmA, cArAssin hAs only moderAte Affinity for rAt tAchykinin binding sites. Possession of An Acidic residue At position 4 AppeArs criticAl for binding to rAt NK-2 sites.
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RAdioiodinAted substAnce P, Neurokinin A, And eledoisin bind predominAntly in NK1 receptors in guineA pig lung.
Molecular pharmacology, 1992Co-Authors: Dominic P. Geraghty, Christian J. Mussap, Elizabeth BurcherAbstract:In homogenAtes of guineA pig lung, binding of 125I-Bolton-Hunter-lAbeled substAnce P (BHSP), Bolton-Hunter-lAbeled eledoisin (BHELE), And [125I]iodohistidyl Neurokinin A (INKA) wAs investigAted. Equilibrium dissociAtion constAnts (derived from "cold" sAturAtion experiments) for BHSP, INKA, And BHELE were 0.96 +/- 0.15, 1.61 +/- 0.26, And 1.98 +/- 0.12 nM, respectively. Specific binding of All three rAdioligAnds wAs increAsed 2-3-fold by 10 microM phosphorAmidon. The rAnk order of potency of unlAbeled tAchykinins in competing AgAinst BHSP wAs substAnce P (SP) greAter thAn [SAr9,Met(O2)11]-SP greAter thAn SP methyl ester greAter thAn neuropeptide gAmmA greAter thAn Neurokinin A greAter thAn or equAl to Neurokinin B = kAssinin greAter thAn or equAl to eledoisin greAter thAn or equAl to scyliorhinin II much greAter thAn neuropeptide K, indicAting binding to sites with the generAl chArActeristics of NK1 receptors. SimilAr rAnk potency orders were observed for INKA And BHELE, showing binding to NK1 sites, rAther thAn to NK2 or NK3 sites, which Are lAbeled with high Affinity by these rAdioligAnds in other tissues. For All rAdioligAnds, competition curves for SP And the NK1-selective Agonist [SAr9,Met(O2)11]-SP could be resolved into two components, representing high And low Affinity binding sites. These were present in the ApproximAte rAtios 2:3 (for BHSP), 1:1 (for INKA), And 8:1 (for BHELE). Other Agonist competition curves Also yielded high And low Affinity components. The dAtA suggest thAt BHSP And INKA bind pArtly And BHELE predominAntly to high Affinity NK1 receptors. The nAture of the low Affinity site(s) could be Another tAchykinin receptor or A low Affinity stAte of the NK1 receptor. Binding to A "clAssicAl" NK2 receptor is unlikely, becAuse selective NK2 receptor AntAgonists And AnAlogs were very weAk competitors. Our dAtA suggest thAt, in Addition to the NK1 receptor, Another type of tAchykinin receptor mAy exist in this tissue. The inAbility to detect NK2 binding sites is strikingly At vAriAnce with functionAl studies.
Thomas Lundeberg - One of the best experts on this subject based on the ideXlab platform.
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effects of repeAted sensory stimulAtion electro Acupuncture And physicAl exercise running on open field behAviour And concentrAtions of neuropeptides in the hippocAmpus in wky And shr rAts
European Journal of Neuroscience, 1996Co-Authors: Violeta Bucinskaite, Elvar Theodorsson, Kevin Crumpton, Carina Stenfors, Anders Ekblom, Thomas LundebergAbstract:The effects of repeAted sensory stimulAtion (electro-Acupuncture) And physicAl exercise (running) on open-field behAviour And on hippocAmpAl concentrAtions of neuropeptide Y, Neurokinin A, substAnce P, gAlAnin And vAsoActive intestinAl peptide (VIP)-like irnmunoreActivities were studied in WKY (WistAr-Kyoto) And SHR (spontAneously hypertensive) rAts. SignificAntly higher concentrAtions of substAnce P-like immunoreActivity , Neurokinin A-like irnrnunoreActivity And neuropeptide Y-like immunoreActivity were found in the hippocAmpus immediAtely After 3 weeks of treAtment (electro-Acupuncture And running), but not 1 week After the lAst (tenth) intervention. No chAnges in gAlAnin-like immunoreActivity And VIP-like immunoreActivity were found. The chAnges in neuropeptide concentrAtions were similAr in the two rAt strAins. Open-field behAviour wAs significAntly reduced during the treAtment period in both strAins. There were significAnt negAtive correlAtions between behAviour And neuropeptide concentrAtions in SHR rAts, suggesting interdependency with sympAthetic Activity. It is proposed thAt the effects of electro-Acupuncture And physicAl exercise in rAts Are relAted to increAses in neuropeptide Y, Neurokinin A And substAnce P in the hippocAmpus.
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substAnce p Neurokinin A cAlcitonin gene relAted peptide And neuropeptide y like immunoreActivity li in rAt knee joint synoviAl fluid during Acute monoArthritis is not correlAted with concentrAtions of neuropeptide li in cerebrospinAl fluid And plAsmA
Neuroscience Letters, 1994Co-Authors: I Bileviciute, Thomas Lundeberg, Anders Ekblom, Elvar TheodorssonAbstract:AbstrAct In A recent study we hAve shown A bilAterAl releAse of substAnce P (SP)-, Neurokinin A (NKA)-, cAlcitonin gene-relAted peptide (CGRP)- And neuropeptide Y (NPY)-like immunoreActivity (-LI) in rAt synoviAl fluid during Acute monoArthritis. In order to elucidAte the mechAnisms underlying these phenomenA, we exAmined the correlAtion between neuropeptide-LI in rAt cerebrospinAl fluid (CSF) And synoviAl fluid And between plAsmA And synoviAl fluid following the intrA-ArticulAr injection of equAl volumes (0.05 ml) of either Freund's AdjuvAns, cArrAgeenAn 2%, substAnce P 10 −5 M or humAn recombinAnt interleukin-1α. Control rAts were given sAline intrA-ArticulArly. CSF, plAsmA And synoviAl fluid from the knee joints were obtAined At 2, 6 And 24 h After injection And were AnAlysed by specific rAdioimmunoAssAys. The intrA-ArticulAr injection of pro-inflAmmAtory substAnces induced chAnges in neuropeptide-LI in synoviAl fluid, CSF And plAsmA. However, there wAs no correlAtion between neuropeptide-LI in synoviAl fluid And plAsmA or between synoviAl fluid And CSF. The results of the present study does not support the hypothesis thAt the bilAterAl chAnges in neuropeptide-LI in synoviAl fluid were due to A releAse of neuropeptides from the inflAmed joint into the systemic circulAtion. However, in cArrAgeenAn induced inflAmmAtion there wAs A tendency towArds A correlAtion in SP-LI between CSF And synoviAl fluid suggesting thAt centrAl neurogenic mechAnisms should be studied in order to explAin the bilAterAl chAnges seen.
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bilAterAl chAnges of substAnce p Neurokinin A cAlcitonin gene relAted peptide And neuropeptide y like immunoreActivity in rAt knee joint synoviAl fluid during Acute monoArthritis
Neuroscience Letters, 1993Co-Authors: I Bileviciute, Thomas Lundeberg, Anders Ekblom, Elvar TheodorssonAbstract:It hAs been hypothetised thAt the nervous system contributes to the symmetricAl response in rheumAtoid Arthritis. In order to elucidAte this, the bilAterAl concentrAtions of substAnce P-like immunoreActivity (SP-LI), Neurokinin A-LI (NKA-LI), cAlcitonin gene-relAted peptide-LI (CGRP-LI) And neuropeptide Y-LI (NPY-LI) in rAt synoviAl fluid during Acute monoArthritis were studied. EquAl volumes (0.05 ml) of either Freund AdjuvAns, cArrAgeenAn 2%, substAnce P 10−5 M or humAn recombinAnt interleukin-1α were injected into the right And sAline into the left knee joint. Control rAts were given sAline bilAterAlly. PerfusAtes were obtAined from both knees simultAneously At 2, 6 And 24 h After injection And were AnAlysed by specific rAdioimmunoAssAys. IncreAse of SP-, NKA-, CGRP-And NPY-LI in synoviAl fluid occurred in both knees After injections with the pro-inflAmmAtory substAnces into the right joints As compAred to controls, except for unchAnged SP-LI in the right knee joint After 24 h following hrIL-1α injection. There wAs, however, generAlly no significAnt difference in the peptide contents between the right knee (injected with pro-inflAmmAtory substAnce) As compAred to the left knee (given sAline) At 2, 6 or 24 h After injection except At three occAsions. The results show thAt experimentAlly induced monoArthritis induces bilAterAl chAnges in synoviAl fluid peptide content.