Characterization of prejunctional 5‐HT 1 receptors that mediate the inhibition of pressor effects elicited by sympathetic stimulation in the pithed rat

1 A study was made of the effects of 5‐carboxamidotryptamine (5‐CT) on pressor responses induced in vivo by electrical stimulation of the sympathetic outflow from the spinal cord of pithed rats. All animals had been pretreated with atropine. Sympathetic stimulation (0.1, 0.5, 1 and 5 Hz) resulted in frequency‐dependent increases in blood pressure. Intravenous infusion of 5‐CT at doses of 0.01, 0.1 and 1 μg kg −1  min −1 reduced the pressor effects obtained by electrical stimulation. The inhibitory effect of 5‐CT was significantly more pronounced at lower frequencies of stimulation. In the present study we characterized the pharmacological profile of the receptors mediating the above inhibitory effect of 5‐CT. 2 The inhibition induced by 0.01 μg kg −1  min −1 of 5‐CT on sympathetically‐induced pressor responses was partially blocked after i.v. treatment with methiothepin (10  μg kg −1 ), WAY‐100,635 (100 μg kg −1 ) or GR127935T (250 μg kg −1 ), but was not affected by cyanopindolol (100 μg kg −1 ). 3 The selective 5‐HT 1A receptor agonist 8‐OH‐DPAT and the selective 5‐HT 1B/1D receptor agonists sumatriptan and L ‐694,247 inhibited the pressor response, whereas the 5‐HT 1B receptor agonists CGS‐12066B and CP‐93,129 and the 5‐HT 2C receptor agonist m ‐CPP did not modify the pressor symapthetic responses. 4 The selective 5‐HT 1A receptor antagonist WAY‐100,635 (100 μg kg −1 ) blocked the inhibition induced by 8‐OH‐DPAT and the selective 5‐HT 1B/1D receptor antagonist GR127935T (250 μg kg −1 ) abolished the inhibition induced either by L ‐694,247 or sumatriptan. 5 None of the 5‐HT receptor agonists used in our experiments modified the pressor responses induced by exogenous noradrenaline (NA). 6 These results suggest that the presynaptic inhibitory action of 5‐CT on the electrically‐induced pressor response is mediated by both r‐5‐HT 1D and 5‐HT 1A receptors.British Journal of Pharmacology (1998) 123 , 1205–1213; doi: 10.1038/sj.bjp.0701714