Comparative analysis of two types of 5-hydroxytryptamine receptor mediating vasorelaxation: differential classification using tryptamines.

摘要: Two receptors mediating relaxant responses to 5-hydroxytryptamine (5-HT) were studied comparatively in rings of rabbit jugular vein contracted with U-46619 (10 nmol/l). At low concentrations 5-HT (0.001–0.1 μmol/l) vascular relaxation was mediated indirectly by the endothelial receptor previously described Leff et al. (1987). In preparations denuded endothelium, higher amine (0.03–30 caused directly, presumably via a located on smooth muscle cells. Similarity between evident that both susceptible antagonism methysergide, but resistant blockade ketanserin and MDL 72222. these respects, qualified for ‘5-HT1-like’ classification. Consistent this, 5-carboxamidotryptamine demonstrated agonist potency than at directly. However, endothelium-intact this order reversed, showing did not satisfy completely criteria designation. When activities single set tryptamines compared -denuded rings, different affinity relative efficacy estimates obtained, confirming two distinct mediate tissue. The most striking difference types α-methyl-5-HT since it expressed high comparable receptor, inactive endothelium-denuded up 30 μmol/l. antagonist studies, butyrophenone spiperone (1 μol/l) likewise distinguished types, failed block endothelium-dependent relaxations, an 8-fold parallel, rightward displacement concentration-effect curve obtained preparations. possibility one or might vasodepressor vivo investigated pentobarbitone-anaesthetised rats treated ketanserin. hypotensive potencies showed close agreement their affinities type directly relaxation, endothelium. mg/kg, i. v.) antagonised response 5-carboxamidotryptamine, causing 10-fold right-shift dose-effect curve. These results further support utility as probes classification and, addition, suggest they can be used differential well vitro.