CHARACTERIZATION OF PREJUNCTIONAL 5-HT1 RECEPTORS THAT MEDIATE THE INHIBITION OF PRESSOR EFFECTS ELICITED BY SYMPATHETIC-STIMULATION IN THEPITHED RAT

1 A study was made of the effects of 5-carboxamidotryptamine (5-CT) on presser responses induced in vivo by electrical stimulation of the sy mpathetic outflow from the spinal cord of pithed rats. All animals had been pretreated with atropine. Sympathetic stimulation (0.1, 0.5, 1 a nd 5 Hz) resulted in frequency-dependent increases in blood pressure. Intravenous infusion of 5-CT at doses of 0.01, 0.1 and 1 mu g kg(-1) m in(-1) reduced the presser effects obtained by electrical stimulation. The inhibitory effect of 5-CT was significantly more pronounced at lo wer frequencies of stimulation. In the present study we characterized the pharmacological profile of the receptors mediating the above inhib itory effect of 5-CT. 2 The inhibition induced by 0.01 mu g kg(-1) min (-1) of 5-CT on sympathetically-induced presser responses was partiall y blocked after i.v. treatment with methiothepin (10 mu g kg(-1)), WAY -100,635 (100 mu g kg(-1)) or GR127935T (250 mu g kg(-1)), but was not affected by cyanopindolol (100 mu g kg(-1)). 3 The selective 5-HT1A r eceptor agonist 8-OH-DPAT and the selective 5-HT1B/1D receptor agonist s sumatriptan and L-694,247 inhibited the presser response, whereas th e 5-HT1B receptor agonists CGS-12066B and CP-93,129 and the 5-HT2C rec eptor agonist m-CPP did not modify the presser sympathetic responses. 4 The selective 5-HT1A receptor antagonist WAY-100,635 (100 mu g kg(-1 )) blocked the inhibition induced by 8-OH-DPAT and the selective 5-HT1 B/1D receptor antagonist GR127935T (250 mu g kg(-1)) abolished the inh ibition induced either by L-694,247 or sumatriptan. 5 None of the 5-HT receptor agonists used in our experiments modified the presser respon ses induced by exogenous noradrenaline (NA). 6 These results suggest t hat the presynaptic inhibitory action of 5-CT on the electrically-indu ced pressor response is mediated by both r-5-HT1D and 5-HT1A receptors .