title: Pharmacological evidence that 5-HT1A/1B/1D, α2-adrenoceptors and D2-like receptors mediate ergotamine-induced inhibition of the vasopressor sympathetic outflow in pithed rats.
abstract: The sympathetic nervous system that innervates the peripheral circulation is regulated by several mechanisms/receptors. It has been reported that prejunctional 5-HT1A, 5-HT1B, 5-HT1D, D2-like receptors and α2-adrenoceptors mediate the inhibition of the vasopressor sympathetic outflow in pithed rats. In addition, ergotamine, an antimigraine drug, displays affinity at the above receptors and may explain some of its adverse/therapeutic effects. Thus, the aims of this study were to investigate in pithed rats: (i) whether ergotamine produces inhibition of the vasopressor sympathetic outflow; and (ii) the major receptors involved in this effect. For this purpose, male Wistar pithed rats were pre-treated with gallamine (25 mg/kg; i.v.) and desipramine (50 µg/kg) and prepared to stimulate the vasopressor sympathetic outflow (T7-T9; 0.03-3 Hz) or to receive i.v. bolus of exogenous noradrenaline (0.03-3 µg/kg). I.v. continuous infusions of ergotamine (1 and 1.8 μg/kgmin) dose-dependently inhibited the vasopressor responses to sympathetic stimulation but not those to exogenous noradrenaline. The sympatho-inhibition elicited by 1.8 μg/kg min ergotamine was (i) unaffected by saline (1 ml/kg); (ii) partially antagonised by WAY 100635 (5-HT1A; 30 μg/kg) and rauwolscine (α2-adrenoceptor; 300 μg/kg), and (iii) dose-dependently blocked by GR 127935 (5-HT1B/1D; 100 and 300 μg/kg) or raclopride (D2-like; 300 and 1000 μg/kg), The above doses of antagonists did not modify per se the sympathetically-induced vasopressor responses. The above results suggest that ergotamine induces inhibition of the vasopressor sympathetic outflow by activation of prejunctional 5-HT1A, 5-HT1B/1D, α2-adrenoceptors and D2-like receptors in pithed rats.
authors: Departamento de Farmacobiología, Cinvestav-Coapa, Czda. de los Tenorios 235, Col. Granjas-Coapa, Deleg. Tlalpan, C.P. 14330 México D.F., México.
authors: Ma Trinidad
authors: MT
authors: Villamil-Hernández
authors: Departamento de Farmacobiología, Cinvestav-Coapa, Czda. de los Tenorios 235, Col. Granjas-Coapa, Deleg. Tlalpan, C.P. 14330 México D.F., México.
authors: Oscar
authors: O
authors: Alcántara-Vázquez
authors: Departamento de Farmacobiología, Cinvestav-Coapa, Czda. de los Tenorios 235, Col. Granjas-Coapa, Deleg. Tlalpan, C.P. 14330 México D.F., México.
authors: Araceli
authors: A
authors: Sánchez-López
authors: Departamento de Farmacobiología, Cinvestav-Coapa, Czda. de los Tenorios 235, Col. Granjas-Coapa, Deleg. Tlalpan, C.P. 14330 México D.F., México.
authors: Erika J
authors: EJ
authors: Gutiérrez-Lara
authors: Departamento de Farmacobiología, Cinvestav-Coapa, Czda. de los Tenorios 235, Col. Granjas-Coapa, Deleg. Tlalpan, C.P. 14330 México D.F., México. Electronic address: dcenturi@cinvestav.mx.
authors: David
authors: D
authors: Centurión
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003891:Desipramine / Q000494:pharmacology; D004878:Ergotamine / Q000494:pharmacology*; D005703:Gallamine Triethiodide / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D044263:Receptors, Serotonin, 5-HT1 / Q000378:metabolism*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D018341:Receptors, Adrenergic, alpha-2; D017448:Receptors, Dopamine D2; D044263:Receptors, Serotonin, 5-HT1; D014662:Vasoconstrictor Agents; D004878:Ergotamine; D005703:Gallamine Triethiodide; D003891:Desipramine; D009638:Norepinephrine
keywords: D(2)-like; Ergotamine; GR 127935; Sympatho-inhibition; WAY 100635; α(2)-adrenoceptors