Tachykinin-induced contraction of the guinea-pig isolated oesophageal mucosa is mediated by NK(2) receptors.
1. The tachykinin receptor present in the guinea-pig oesophageal mucosa that mediates contractile responses of the muscularis mucosae has been characterized, using functional in vitro experiments. 2. The NK(1) receptor-selective agonist, [Sar(9)(O(2))Met(11)]SP and the NK(3) receptor-selective agonists, [MePhe(7)]-NKB and senktide, produced no response at submicromolar concentrations. The NK(2) receptor-selective agonists, [Nle(10)]-NKA(4 - 10), and GR 64,349 produced concentration-dependent contractile effects with pD(2) values of 8.20+/-0.16 and 8.30+/-0.15, respectively. 3. The concentration-response curve to the non-selective agonist, NKA (pD(2)=8.13+/-0.04) was shifted significantly rightwards only by the NK(2) receptor-selective antagonist, GR 159,897 and was unaffected by the NK(1) receptor-selective antagonist, SR 140,333 and the NK(3) receptor-selective antagonist, SB 222,200. 4. The NK(2) receptor-selective antagonist, GR 159,897, exhibited an apparent competitive antagonism against the NK(2) receptor-selective agonist, GR 64,349 (apparent pK(B) value=9.29+/-0.16) and against the non-selective agonist, NKA (apparent pK(B) value=8.71+/-0.19). 5. The NK(2) receptor-selective antagonist, SR 48,968 exhibited a non-competitive antagonism against the NK(2) receptor-selective agonist, [Nle(10)]-NKA(4 - 10). The pK(B) value was 10.84+/-0.19.6. It is concluded that the guinea-pig isolated oesophageal mucosa is a useful preparation for studying the effects of NK(2) receptor-selective agonists and antagonists as the contractile responses to various tachykinins are mediated solely by NK(2) receptors.
Kerr
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Department of Pharmaceutical Biology and Pharmacology, Victorian College of Pharmacy, Monash University, 381 Royal Parade, Parkville, Victoria 3052, Australia.
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D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004947:Esophagus / Q000187:drug effects* / Q000502:physiology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009092:Mucous Membrane / Q000187:drug effects* / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects*; D015288:Neurokinin A / Q000031:analogs & derivatives / Q000494:pharmacology; D015287:Neurokinin B / Q000031:analogs & derivatives* / Q000494:pharmacology; D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D011812:Quinuclidines / Q000494:pharmacology; D018040:Receptors, Neurokinin-1 / Q000819:agonists; D018041:Receptors, Neurokinin-2 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D018042:Receptors, Neurokinin-3 / Q000819:agonists / Q000037:antagonists & inhibitors; D013373:Substance P / Q000031:analogs & derivatives* / Q000494:pharmacology; D015320:Tachykinins / Q000494:pharmacology*; D015244:Thiorphan / Q000494:pharmacology
D001549:Benzamides; D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments; D010880:Piperidines; D011480:Protease Inhibitors; D011804:Quinolines; D011812:Quinuclidines; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; D018042:Receptors, Neurokinin-3; C109112:SB 222200; D015320:Tachykinins; C080394:neurokinin B, MePhe(7)-; C054724:senktide; C061060:neurokinin A (4-10), Nle(10)-; C062618:substance P, Sar(9)-Met(O2)(11)-; C068031:neurokinin A (3-10), lysyl(3)-glycyl(8)-R-lactam-leucine(9)-; C085215:SR 140333; D013373:Substance P; C073839:SR 48968; D015288:Neurokinin A; D015287:Neurokinin B; D002216:Captopril; D015244:Thiorphan