Tachykinin-induced contraction of the guinea-pig isolated oesophageal mucosa is mediated by NK(2) receptors

• Published in: British journal of pharmacology Vol. 131; no. 7; pp. 1461 - 1467
• Main Authors: Kerr, K P, Thai, B, Coupar, I M
• Format: Journal Article
• Language: English
• Published: England 01.12.2000
• Subjects: Animals; Benzamides - pharmacology; Captopril - pharmacology; Dose-Response Relationship, Drug; Esophagus - drug effects; Esophagus - physiology; Guinea Pigs; In Vitro Techniques; Mucous Membrane - drug effects; Mucous Membrane - physiology; Muscle Contraction - drug effects; Neurokinin A - analogs & derivatives; Neurokinin A - pharmacology; Neurokinin B - analogs & derivatives; Neurokinin B - pharmacology; Neurokinin-1 Receptor Antagonists; Peptide Fragments - pharmacology; Piperidines - pharmacology; Protease Inhibitors - pharmacology; Quinolines - pharmacology; Quinuclidines - pharmacology; Receptors, Neurokinin-1 - agonists; Receptors, Neurokinin-2 - agonists; Receptors, Neurokinin-2 - antagonists & inhibitors; Receptors, Neurokinin-2 - physiology; Receptors, Neurokinin-3 - agonists; Receptors, Neurokinin-3 - antagonists & inhibitors; Substance P - analogs & derivatives; Substance P - pharmacology; Tachykinins - pharmacology; Thiorphan - pharmacology
• ISSN: 0007-1188

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.