Characterization of prejunctional 5-HT1 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 mg 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 microg kg(-1) min(-1) of 5-CT on sympathetically-induced pressor responses was partially blocked after i.v. treatment with methiothepin (10 microg kg(-1)), WAY-100,635 (100 microg kg(-1)) or GR127935T (250 microg kg(-1)), but was not affected by cyanopindolol (100 microg kg(-1)). 3. The selective 5-HT1A 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-HT1B receptor agonists CGS-12066B and CP-93,129 and the 5-HT2C receptor agonist m-CPP did not modify the pressor sympathetic responses. 4. The selective 5-HT1A receptor antagonist WAY-100,635 (100 microg kg(-1)) blocked the inhibition induced by 8-OH-DPAT and the selective 5-HT(1B/1D) receptor antagonist GR127935T (250 microg 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-HT1D and 5-HT1A receptors.
Morán
A
A
Departamento de Fisiología y Farmacología, Facultad de Farmacia, Universidad de Salamanca, Spain.
Fernández
M M
MM
Velasco
C
C
Martín
M L
ML
San Román
L
L
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004558:Electric Stimulation; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017661:Receptors, Presynaptic / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism*; D012701:Serotonin / Q000031:analogs & derivatives* / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology
D017661:Receptors, Presynaptic; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin; C047087:5-carboxamidotryptamine; D009638:Norepinephrine