Effect of 5-hydroxytryptamine on neurogenic vasoconstriction in the isolated, autoperfused hindquarters of the rat.
1. In the present study, we analysed the effect of different doses of 5-hydroxytryptamine (5-HT; intravenous infusions of 0.001-40 microg/kg per min) in the autoperfused hindquarters of the rat subjected to electrical stimulation (frequencies of 0.5-20 Hz) of the lumbar chains, investigating the relationship between the adrenergic and serotonergic systems in this vascular bed. 2. Because we observed that 5-HT inhibited the increases in perfusion pressure induced by electrical stimulation of the lumbar chains, we used different agonists and antagonists to analyse the mechanism of action of 5-HT. 3. The effect of 5-HT was inhibited by methiothepin (a non-specific 5-HT receptor antagonist), but not by ritanserin (a selective 5-HT2 receptor antagonist). The effects of 5-HT were mimicked by 5-carboxamidotryptamine (a 5-HT1 receptor agonist) and L-694 247 (a selective 5-HT1D receptor agonist), but not by 8-hydroxy-2-dipropylaminotetralin (a 5-HT1A receptor agonist), CGS-12066B (a 5-HT1B receptor agonist), alpha-methyl-5-HT (a 5-HT2 receptor agonist), 1-(3-chlorophenyl) piperazine (a 5-HT2C receptor agonist) or 1-phenylbiguanide (a 5-HT3 receptor agonist). The selective 5-HT1D/1B receptor antagonist BRL 15572 inhibited the effect of the agonist L-694 247. 4. Our data suggest that 5-HT inhibits the increases in perfusion pressure induced by the electrical stimulation of the lumbar chains, acting on presynaptic 5-HT1D receptors and decreasing the release of noradrenaline from the sympathetic nerves in the hindquarter vascular bed of the rat.
Calama
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Laboratorio de Farmacognosia y Farmacología, Departamento de Fisiología y Farmacología, Facultad de Farmacia, Universidad de Salamanca, Campus Miguel de Unamuno, Salamanca, Spain.
Ortíz de Urbina
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AV
Morán
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Martín
M L
ML
San Román
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L
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D001645:Biguanides / Q000819:agonists; D001713:Biphenyl Compounds / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006614:Hindlimb / Q000098:blood supply / Q000187:drug effects / Q000294:innervation; D066298:In Vitro Techniques; D007262:Infusions, Intravenous; D008297:Male; D008719:Methiothepin / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D010477:Perfusion; D010879:Piperazines / Q000494:pharmacology; D011312:Pressure; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D016713:Ritanserin / Q000494:pharmacology; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology*; D058825:Serotonin 5-HT1 Receptor Agonists; D058826:Serotonin 5-HT2 Receptor Agonists; D058827:Serotonin 5-HT3 Receptor Agonists; D018490:Serotonin Agents / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D014363:Tryptamines / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*
D001645:Biguanides; D001713:Biphenyl Compounds; D010069:Oxadiazoles; D010879:Piperazines; D011810:Quinoxalines; D058825:Serotonin 5-HT1 Receptor Agonists; D058826:Serotonin 5-HT2 Receptor Agonists; D058827:Serotonin 5-HT3 Receptor Agonists; D018490:Serotonin Agents; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D014363:Tryptamines; C052561:CGS 12066B; C085632:L 694247; D016713:Ritanserin; C042390:alpha-methylserotonin; D012701:Serotonin; D008719:Methiothepin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C047087:5-carboxamidotryptamine; C108532:BRL 15572; C015068:1-(3-chlorophenyl)piperazine; C008846:phenyl biguanide