1 A study was made of the e ects of 5-carboxamidotryptamine (5-CT) on pressor responses induced in vivo by electrical stimulation of the sympathetic out¯ow 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 frequencydependent increases in blood pressure. Intravenous infusion of 5-CT at doses of 0.01, 0.1 and 1 mg kg 71 min 71 reduced the pressor e ects obtained by electrical stimulation. The inhibitory e ect of 5-CT was signi®cantly more pronounced at lower frequencies of stimulation. In the present study we characterized the pharmacological pro®le of the receptors mediating the above inhibitory e ect of 5-CT. 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.

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1. In a previous study, we showed that the presynaptic inhibitory action of 5-hydroxytryptamine receptor agonists on sympathetic pressor effects obtained in the pithed rats were mainly mediated by activation of 5-HT1A and 5-HT1D receptor subtypes. At the time, we observed that some 5-HT1 receptors antagonists - WAY 100,635 and NAN-190 (both 5-HT1A receptor antagonists), methiothepin (a 5-HT1,2,5,6,7 receptor antagonist) and spiperone (a 5-HT1,2 receptor antagonist) - reduced per se the pressor effects obtained by electrical stimulation. The aim of the present work was to investigate the mechanism participating in this inhibitory effect. 2. The inhibition induced by WAY 100,635 (1000 microg kg-1, i.v.) was blocked after i.v. treatment with idazoxan, an alpha2-adrenoceptor antagonist (300 and 1000 microg kg-1) and was not modified after i.v. treatment with propranolol, a beta-adrenoceptor antagonist (1000 microg kg-1) and sulpiride, a D2 receptor antagonist (1000 microg kg-1). The inhibition induced by spiperone (500 microg kg-1 i.v.) was significantly blocked by sulpiride (1000 microg kg-1) and was not modified by idazoxan or propranolol. 3. Sulpiride (1000 microg kg-1) partially blocked the inhibition induced by methiothepin (50 microg kg-1 i.v.). Only pretreatment with idazoxan (300 microg kg-1) modified the inhibition induced by NAN-190 (100 microg kg-1 i.v.), such inhibition increasing after intravenous administration of idazoxan. 4. All the antagonists used in our experiments failed to inhibit the pressor responses elicited by i.v. noradrenaline administration. 5. The above results suggest that the inhibitory effects of these 5-HT1 receptor 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.

In the present study we attempted to characterise the responses and receptors involved in the effects of 5-hydroxytryptamine (5-HT, serotonin) in in situ autoperfused rat hindquarters. Intra-arterial administration of the lowest doses of 5-HT used (0.12-12.5 ng/kg) induced vasodilator responses, whereas the highest doses (25-1000 ng/kg) produced vasoconstriction. The vasodilator effect was inhibited by methiothepin (a non-specific 5-HT(1,2,5,6,7) receptor antagonist) and by a 5-HT(1D/1B) receptor antagonist, i.e., 3-[4-(4-chlorophenyl)piperazin-1-yl]-1,1-diphenyl-2-propanolol (BRL 15572), but not by ritanserin (a selective 5-HT(2) receptor antagonist), 5-methyl-1-(3-pyridylcarbamoyl)-1,2,3,5-tetrahydropyrrolo[2,3-f] indole (SB 206553, a selective 5-HT(2B/2C) receptor antagonist) or mesulergine (a non-specific serotonergic antagonist that shows affinity to the 5-HT(7) receptor). This vasodilator effect was mimicked by administration of a selective 5-HT(1) receptor agonist - 5-carboxamidotryptamine (5-CT) - and by 2-[5-[3-(4-methylsulphonylamino)benzyl-1,2,4-1 H-indol-3-yl]ethanamine (L-694,247, a selective 5-HT(1D/1B) receptor agonist). Methiothepin, but not mesulergine, inhibited 5-CT-induced vasodilatation and the selective 5-HT(1D/1B) receptor antagonist (BRL 15572) inhibited the vasodilator action induced by L-694,247. The vasoconstrictor effect of 5-HT was significantly decreased by methiothepin, ritanserin and SB 206553, and was mimicked by alpha-methyl-5-HT (a selective 5-HT(2) receptor agonist) but not by administration of BW 723C86, a selective 5HT(2B) receptor agonist. Ritanserin, SB 206553 and spiperone (a non-specific 5-HT(1/2A) receptor antagonist) inhibited the alpha-methyl-5HT-induced vasoconstriction.Our data suggest that the vasodilator response induced by 5-HT in autoperfused rat hindquarters is mainly mediated by 5-HT(1D/1B) receptors, whereas the vasoconstrictor effect is mainly due to the activation of 5-HT(2A) receptors.