5-HYDROXYTRYPTAMINE-INDUCED CONTRACTION OF THE MARMOSET AORTA IS MEDIATED BY A 5-HT1-LIKE RECEPTOR

1. 5-Hydroxytryptamine (5-HT) exerts both contractile and relaxant eff ects in the marmoset isolated aorta, actions that are unaffected by th e 5-HT2 antagonist ketanserin. The aim of the present study was to def ine the receptors mediating the contractile activity of 5-HT in the ma rmoset aorta, 2. Contractile responses were elicited in aortic rings t hat were either: (i) precontracted submaximally with the thromboxane A (2) agonist U44069 in order to amplify the responses; or (ii) exposed to N-omega-nitro-L-arginine (100 mu mol/L) plus LY 53857 (0.1 mu mol/L ; a 5-HT2 receptor antagonist shown previously to inhibit relaxation), The effect of 5-HT on adenosine 3',5'-cyclic monophosphate (cAMP) for mation was also investigated, 3. The effects of agonists and antagonis ts comprised: (i) agonist potencies in the order 5-carboxamidotryptami ne > 5-HT > sumatriptan > 8-hydroxy-2-(di-n-propylamino)tetralin; (ii) inhibition of contractile action of 5-HT by the 5-HT1D antagonist GR 127935; (iii) a contractile response to methysergide; (iv) a lack of e ffect of tropisetron, an antagonist of 5-HT3 and 5-HT4 receptors; and (v) inhibition of forskolin-stimulated cAMP formation by 5-HT (in the presence of LY 53857), indicative of negative coupling to adenylate cy clase, 4. The above effects fulfil the criteria for a 5-HT1-like recep tor, In view of the previous finding that this contractile response is insensitive to ketanserin, it is concluded that the contractile effec ts of 5-HT in the marmoset aorta are mediated exclusively by a 5-HT1-l ike receptor.