Receptors Involved in the Modulation of 5-Hydroxytryptamine Release in Bovine Cerebral Arteries

Abstract

The uptake of [3H]5-hydroxytryptamine (5-HT) in bovine cerebral arteries was reduced by cocaine (1 μM), ouabain (100 μM), pretreatment with 6-hydroxydopamine (6-OHDA) (1·46 MM, 10 min) and metitepine (1 μM). Electrically-stimulated tritium release was decreased by tetrodotoxin (0·8 μM), Ca-free medium, denervation with 6-OHDA (1·46 MM, 10 min), 5-HT (10 μM), noradrenaline (1 μM) and the agonist of α2-adrenoceptors B-HT 920 (0·1 and 1 μM), enhanced by metitepine (1 μM, antagonists of presynaptic 5-HT1 receptors) and rauwolscine (1 μM, antagonist at α2-adrenoceptors, and also of 5-HT,1D receptors) and not affected by ketanserin (1 μM, antagonist of 5-HT2 receptors), methysergide (0·1 μM, antagonist of 5-HT1 and 5-HT2 receptors) and phentolamine (1 and 3 μM antagonist of α-adrenoceptors and less potent of 5-HT1 receptors). The inhibitory action of 10 μM 5-HT was partially reversed by phentolamine (3 μM) and cocaine (1 μM) and completely reversed by both metitepine (1 μM) and rauwolscine (1 μM). Ketanserin (1 μM), methysergide (0·1 μM) or phentolamine (1 μM) had no effect. Rauwolscine (1 μM) antagonized the inhibition induced by both noradrenaline (1 μM) and B-HT 920 (0·1 and 1 μM). 5-HT induced tritium release which was inhibited by cocaine (an antagonist of 5-HT3 receptors) and denervation with 6-OHDA. These results suggest that 5-HT is mainly accumulated in adrenergic nerve endings, that evoked [3H]5-HT release is modulated by 5-HT1-like receptors, but the participation of α2-adrenoceptors cannot be discounted, or more probably both types of receptors have features in common, and evoked [3H]5-HT release elicited by 5-HT may be partially mediated by activation of 5-HT3 receptors.