Format

Send to

Choose Destination
Br J Pharmacol. 2000 Jun;130(3):692-8.

Further evidence that 5-HT-induced relaxation of pig pulmonary artery is mediated by endothelial 5-HT(2B) receptors.

Author information

1
Center for Vascular Biology and Medicine, Friedrich-Schiller-University Jena, Nordhäuser Strasse 78, D-99089 Erfurt, Germany. Glusa@zmkh.ef.uni-jena.de

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.

PMID:
10821800
PMCID:
PMC1572101
DOI:
10.1038/sj.bjp.0703341
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center