Characterization of receptors mediating contraction induced by tachykinins in the guinea-pig isolated common bile duct

British Journal of Pharmacology
R PatacchiniC A Maggi

Abstract

1. We studied the effect of the natural tachykinins and of synthetic agonists selective for the tachykinin NK1, NK2 and NK3 receptors, on the motility of guinea-pig isolated common bile duct longitudinally-oriented smooth muscle. 2. All the tachykinins tested (both natural and synthetic) produced a concentration-dependent contractile response of the guinea-pig isolated common bile duct: these effects underwent a marked tachyphylaxis, especially the responses elicited by NK1 and NK3 receptor-selective agonists. 3. Among the natural tachykinins neurokinin B (EC50 = 3.2 nM; 95% c.l. = 2.0-5.1; n = 4) was the most potent, being about 40 and 25 fold more potent than substance P (EC50 = 121.6 nM; 95% c.l. = 94-157; P < 0.01; n = 4) and neurokinin A (EC50 = 83.4 nM; 95% c.l. = 62-112; P < 0.01; n = 4), respectively. Among the synthetic analogues the NK3 receptor-selective agonist senktide (EC50 = 1.1 nM; 95% c.l. = 0.7-1.8; n = 8) was the most potent, being about 120, 110 and 20 fold more potent than [Sar9]substance P sulfone (NK1 receptor-selective) (EC50 = 130.4 nM; 95% c.l. = 99-172; P < 0.01; n = 8), [beta Ala8]NKA (4-10) (NK2 receptor-selective) (EC50 = 120.1 nM; 95% c.l. = 95-151; P < 0.01; n = 8) and septide (NK1 receptor-selec...Continue Reading

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Citations

Apr 29, 2000·Trends in Pharmacological Sciences·R PatacchiniP Holzer
Jul 21, 2004·Biomedical Engineering Online·Birgitte U DuchHans Gregersen
Mar 12, 2008·HPB : the Official Journal of the International Hepato Pancreato Biliary Association·Y SonodaG T P Saccone
May 8, 2018·The Journal of Pharmacology and Experimental Therapeutics·Nadia M J RupniakEdward C Burgard
Jan 2, 2020·Scientific Reports·Tove J GrönroosOlof Solin

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