title: 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.
abstract: 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 α-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 μg/kg (but not 100 μg/kg) GR127935 (5-HT(1A/1B/1D/1F)) abolished the inhibition to sumatriptan, indorenate, PNU-142633 or LY344864; (ii) 310 μg/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 μg/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.
authors.affiliation: Departamento de Farmacobiología, Cinvestav-Coapa, Czda. de los Tenorios 235, Col. Granjas-Coapa, Deleg. Tlalpan, 14330 México D.F., Mexico.
authors.forename: Abimael
authors.initials: A
authors.lastname: González-Hernández
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Manrique-Maldonado
authors.forename: Jair
authors.initials: J
authors.lastname: Lozano-Cuenca
authors.forename: Enriqueta
authors.initials: E
authors.lastname: Muñoz-Islas
authors.forename: David
authors.initials: D
authors.lastname: Centurión
authors.forename: Antoinette
authors.initials: A
authors.lastname: Maassen VanDenBrink
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Villalón
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism* / Q000494:pharmacology; D004558:Electric Stimulation; D006439:Hemodynamics / Q000187:drug effects; D008024:Ligands; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism; D044346:Receptor, Serotonin, 5-HT1D / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism; D044263:Receptors, Serotonin, 5-HT1 / Q000378:metabolism*; D058825:Serotonin 5-HT1 Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology; D058829:Serotonin 5-HT1 Receptor Antagonists / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D000096642:Receptor, Serotonin, 5-HT1F
chemical_list: D015740:Calcitonin Gene-Related Peptide; D008024:Ligands; D044282:Receptor, Serotonin, 5-HT1A; D044346:Receptor, Serotonin, 5-HT1D; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D000096642:Receptor, Serotonin, 5-HT1F