The actions of 5-hydroxytryptamine receptor agonists and antagonists at pre- and postjunctional level on the canine saphenous vein

Abstract

The prejunctional and postjunctional 5-HT receptors of the canine saphenous vein were studied. The release of 3H-noradrenaline (3H-NA) from incubated saphenous vein strips was inhibited by 5-hydroxytryptamine (5-HT) in a concentration-dependent way (5-HT concentrations: 0.01, 0.1 and 1.0 mumol.l-1), but not by the selective 5-HT1A agonist 8-hydroxy-dipropylaminotetralin (8-OH-DPAT; 1 and 10 mumol.l-1). The inhibitory effect of 5-HT was antagonized by metitepine and methysergide, but not by yohimbine, (-)-pindolol or ketanserin. In strips preincubated with 5-HT (1.2 mumol.l-1), the fractional release of 3H-NA was slightly reduced (paired experiments). 5-HT and 8-OH-DPAT caused concentration-dependent contractions of the saphenous smooth muscle. A parallel shift of the concentration-response curve for 8-OH-DPAT to the right was caused by metitepine and yohimbine, but not by ketanserin. The contractions caused by 5-HT were antagonized by metitepine and yohimbine (parallel displacement of the curves to the right), as well as by ketanserin and methysergide (with a depression of the upper part of the curve). Blockade of alpha-adrenoceptors (due to prazosin plus a low concentration of yohimbine) also resulted in a weak antagonistic effect. Ketanserin and metitepine displaced the noradrenaline concentration-response curve to the right. We conclude that the saphenous vein of the dog is endowed with prejunctional receptors of the 5-HT1 type which can not be classified as belonging either to the 1A or 1B subtype; and that at the postjunctional level 5-HT1 (possibly of the 1D subtype) and 5-HT2 receptors are present.(ABSTRACT TRUNCATED AT 250 WORDS)