Characterization of mechanisms involved in presynaptic inhibition of sympathetic presser effects induced by some 5-HT1 receptor antagonists

1 In a previous study, we showed that the presynaptic inhibitory action of 5-hydroxytryptamine receptor agonists on sympathetic presser effects obtain ed in the pithed rats were mainly mediated by activation of 5-HT1A and 5-HT 1D receptor subtypes. At the time, we observed that some 5-HT1 receptors an tagonists - WAY 100,635 and NAN-190 (both S-HT1A receptor antagonists), met hiothepin (a 5-HT1,2,5,6,7 receptor antagonist) and spiperone (a 5-HT1,2 re ceptor antagonist) - reduced per se the presser effects obtained by electri cal stimulation. The aim of the present work was to investigate the mechani sm participating in this inhibitory effect. 2 The inhibition induced by WAY 100,635 (1000 mug kg(-1), i.v.) was blocked after i.v. treatment with idazoxan, an alpha (2)-adrenoceptor antagonist ( 300 and 1000 mug kg(-1)) and was not modified after i.v. treatment with pro pranolol, a beta -adrenoceptor antagonist (1000 mug kg(-1)) and sulpiride, a D-2 receptor antagonist (1000 mug kg(-1)). The inhibition induced by spip erone (500 mug kg(-1) i.v.) was significantly blocked by sulpiride (1000 mu g kg(-1)) and was not modified by idazoxan or propranolol. 3 Sulpiride (1000 mug kg(-1)) partially blocked the inhibition induced by m ethiothepin (50 mug kg(-1) i.v.). Only pretreatment with idazoxan (300 mug kg(-1)) modified the inhibition induced by NAN-190 (100 mug kg(-1) i.v.), s uch inhibition increasing after intravenous administration of idazoxan. 4 All the antagonists used in our experiments failed to inhibit the presser responses elicited by i.v. noradrenaline administration. 5 The above results suggest that the inhibitory effects of these 5-HT1 rece ptor antagonists are presynaptic in nature, but not related to the blockade of 5-HT1 receptors subtypes. The simultaneous activation or inhibition of other receptor systems could explain the inhibition produced by each 5-HT1 receptor antagonist studied.