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The 5-HT(1) receptors inhibiting the rat vasodepressor sensory CGRPergic outflow: further involvement of 5-HT(1F), but not 5-HT(1A) or 5-HT(1D), subtypes

We have previously shown that 5-HT(1B) receptors inhibit prejunctionally the rat vasodepressor CGRPergic sensory outflow. Since 5-HT(1) receptors comprise 5-HT(1A), 5-HT(1B), 5-HT(1D) and 5-HT(1F) functional subtypes, this study has further investigated the role of 5-HT(1A), 5-HT(1D) and 5-HT(1F) receptor subtypes in the inhibition of the above vasodepressor sensory outflow. Pithed rats were pretreated with i.v. continuous infusions of hexamethonium and methoxamine, followed by 5-HT(1) receptor agonists. Then electrical spinal stimulation (T(9)-T(12)) or i.v. bolus injections of exogenous alpha-CGRP produced frequency-dependent or dose-dependent vasodepressor responses. The electrically-induced vasodepressor responses remained unchanged during infusions of the 5-HT(1A) receptor agonists 8-OH-DPAT and NN-DP-5-CT. In contrast, these responses were inhibited by the agonists sumatriptan (5-HT(1A/1B/1D/1F)), indorenate (5-HT(1A)), PNU-142633 (5-HT(1D)) or LY344864 (5-HT(1F)), which did not affect the vasodepressor responses to exogenous CGRP (implying a prejunctional sensory-inhibition). When analysing the effects of antagonists: (i) 310 mug/kg (but not 100 mug/kg) GR127935 (5-HT(1A/1B/1D/1F)) abolished the inhibition to sumatriptan, indorenate, PNU-142633 or LY344864; (ii) 310 mug/kg SB224289 (5-HT(1B)) or BRL15572 (5-HT(1D)) failed to block the inhibition to sumatriptan or PNU-142633, whereas SB224289+BRL15572 partly blocked the inhibition to sumatriptan; and (iii) 10 mug/kg WAY100635 (5-HT(1A)) failed to block the inhibition to indorenate. These results suggest that 5-HT(1F), but not 5-HT(1A) or 5-HT(1D), receptor subtypes inhibit the vasodepressor sensory CGRPergic outflow although, admittedly, no selective 5-HT(1F) receptor agonist is available yet. The pharmacological profile of these receptors resembles that shown in rat dorsal root ganglia by molecular biology techniques

Keywords : administration & dosage,agonists,Animals,Calcitonin Gene-Related Peptide,drug effects,Electric Stimulation,Hemodynamics,Injections,Ligands,Male,metabolism,pharmacology,Rats,Rats,Wistar,Receptor,Serotonin,5-HT1A,Receptor,Serotonin,5-HT1D,Receptors,Serotonin,Receptors,Serotonin,5-HT1,Serotonin 5-HT1 Receptor Agonists,Serotonin 5-HT1 Receptor Antagonists,Vasodilation,, 5ht(1),Receptors,Inhibiting,Rat, atypical trigeminal neuralgia surgery

Date of Publication : 2011 Jun 1

Authors : Gonzalez-Hernandez A;Manrique-Maldonado G;Lozano-Cuenca J;Munoz-Islas E;Centurion D;Maassen VA;Villalon CM;

Organisation : Departamento de Farmacobiologia, Cinvestav-Coapa, Czda. de los Tenorios 235, Col. Granjas-Coapa, Deleg. Tlalpan, 14330 Mexico D.F., Mexico

Journal of Publication : Eur J Pharmacol

Pubmed Link : https://www.ncbi.nlm.nih.gov/pubmed/21473863

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