Further evidence that 5‐HT‐induced relaxation of pig pulmonary artery is mediated by endothelial 5‐HT2B receptors
Year: 2000
Type: article
Abstract: The endothelial 5-HT receptor mediating relaxation of pig pulmonary artery has been characterized using the selective 5-HT(2B) receptor agonist BW 723C86 and a variety of structurally diverse 5-HT receptor antagonists. If arterial rings with intact endothelium were precontracted with prostaglandin F(2alpha) (3 microM), BW 723C86 caused concentration-dependent relaxation with a pEC(50)=8.21+/-0.03 and E(max)=89+/-4% relative to 5-HT. The relaxant responses to BW 723C86 were inhibited by the 5-HT(2B) receptor antagonist SB 204741, the 5-HT(2B/2C) receptor antagonist SB 206553 and the antimigraine drug pizotifen, yielding pA(2) values of 6.68, 7.20 and 8.32, respectively. The pA(2) values against BW 723C86 were similar to those determined against 5-HT. The relaxant effect of 5-HT was antagonized by a variety of 22 compounds of diverse chemical structures. Based on the calculated mean pA(2) values the order of the most potent antagonists was ritanserin (9.38) > methysergide (8. 86) > pizotifen (8.47) >/= methiothepin (8.32) > LY 53857 (7.84) >/= amoxapine (7.80) >/= loxapine (7.73) >/= metergoline (7.64) >/= mianserin (7.51) >/= rauwolscine (7.39). Compounds with weak blocking potency were yohimbine (6.37), spiperone (5.88) and ketanserin (5.85). Correlation analysis between the affinities of the antagonists in pig pulmonary artery and those from radioligand binding studies at human and rat 5-HT(2B) receptors showed a highly significant correlation (r=0.95 and 0.84, P<0.002 and <0.005). Correlation with 5-HT(2C) receptors was much lower (r=0.57, P=0.035), and no correlations were obtained with 5-ht(6) and 5-HT(7) receptors. It is concluded that the 5-HT receptor mediating endothelium-dependent relaxation of pig pulmonary artery is of the 5-HT(2B) subtype.
Source: British Journal of Pharmacology
Institutions: Friedrich Schiller University Jena, Freie Universität Berlin
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W2086990019