PRESYNAPTIC 5-HYDROXYTRYPTAMINE RECEPTORS MODULATING NORADRENALINE RELEASE IN BOVINE CEREBRAL-ARTERIES

The electrical stimulation of bovine cerebral arteries preincubated wi th [H-3]-noradrenaline (NA) evoked tritium overflow, which was reduced by tetrodotoxin, Ca2+-free medium and denervation by pretreatment wit h 6-hydroxydopamine. 2 The evoked tritium overflow was reduced by non- selective, 5-hydroxytryptamine (5-HT), and selective, 5-carboxamidotry ptamine (5-CT) and sumatriptan, agonists of 5-HT1-like receptors, the latter with certain preference for the 5-HT1D subtype. This overflow w as also reduced by NA and B-HT 920 (non-selective and selective agonis ts of alpha2-adrenoceptors), enhanced by metitepine (antagonist of 5HT 1 and 5-HT2 receptors), and unaltered by ketanserin (antagonist of 5-H T2 receptors), methysergide (antagonist of 5-HT1 and 5-HT2 receptors) and phentolamine (antagonist of alpha- and 5-HT1 receptors). The metit epine increase was blocked by cocaine and phentolamine. 3 The release- inhibiting effect of 5-HT was reduced by cocaine, metitepine, phentola mine and methysergide, but not by ketanserin. Metitepine reversed the inhibition caused by 5-CT and sumatriptan. Metitepine, methysergide an d phentolamine antagonized the inhibition of the tritium overflow elic ited by B-HT 920. 4 These results suggest: (1) the evoked NA release i s modulated by 5-HT1-like receptors, likely to be of 5-HT1D subtype; a nd (2) metitepine has also the ability to block NA uptake and to antag onize presynaptic a2-adrenoceptors.