title: Clonidine inhibits the canine external carotid vasodilatation to capsaicin by alpha2A/2C-adrenoceptors.
abstract: Migraine is a disorder associated with increased plasma concentrations of calcitonin gene-related peptide (CGRP). CGRP, a neuropeptide released from activated trigeminal sensory nerves, dilates cranial blood vessels and transmits vascular nociception. Moreover, several antimigraine drugs inhibit the dural neurogenic vasodilatation to trigeminal stimulation. Hence, this study investigated in anaesthetized dogs the effects of the alpha(2)-adrenoceptor agonist, clonidine, on the external carotid vasodilator responses to capsaicin, alpha-CGRP and acetylcholine. 1-min intracarotid infusions of capsaicin (10, 18, 30 and 56 microg/min), alpha-CGRP (0.1, 0.3, 1 and 3 microg/min) and acetylcholine (0.01, 0.03, 0.1 and 0.3 microg/min) produced dose-dependent increases in external carotid conductance without affecting blood pressure or heart rate. Interestingly, the carotid vasodilator responses to capsaicin, but not those to alpha-CGRP or acetylcholine, were partially inhibited after clonidine (total dose: 24.4 microg/kg, i.v.); in contrast, equivalent volumes of saline did not affect the responses to capsaicin, alpha-CGRP or acetylcholine. The inhibitory responses to clonidine were antagonized by i.v. administration of the alpha(2)-adrenoceptor antagonists rauwolscine (alpha(2A/2B/2C); 300 microg/kg), BRL44408 (alpha(2A); 1000 microg/kg) or MK912 (alpha(2C); 100 and 300 microg/kg), but not by imiloxan (alpha(2B); 1000 microg/kg). These results suggest that clonidine inhibits the external carotid vasodilator responses to capsaicin by peripheral trigeminovascular and/or central mechanisms; this inhibitory response to clonidine seems to be predominantly mediated by alpha(2A)-adrenoceptors and, to a much lesser extent, by alpha(2C)-adrenoceptors.
authors.affiliation: Departamento de Farmacobiología, Cinvestav-Coapa, Czda. de los Tenorios 235, Col. Granjas-Coapa, Deleg. Tlalpan, C.P. 14330, México DF, México.
authors.forename: Luisa R
authors.initials: LR
authors.lastname: Jiménez-Mena
authors.forename: Saurabh
authors.initials: S
authors.lastname: Gupta
authors.forename: Enriqueta
authors.initials: E
authors.lastname: Muñoz-Islas
authors.forename: Jair
authors.initials: J
authors.lastname: Lozano-Cuenca
authors.forename: Araceli
authors.initials: A
authors.lastname: Sánchez-López
authors.forename: David
authors.initials: D
authors.lastname: Centurión
authors.forename: Suneet
authors.initials: S
authors.lastname: Mehrotra
authors.forename: Antoinette
authors.initials: A
authors.lastname: MaassenVanDenBrink
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Villalón
mesh_terms: D000109:Acetylcholine / Q000037:antagonists & inhibitors; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors; D002211:Capsaicin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D002342:Carotid Artery, External / Q000187:drug effects* / Q000378:metabolism; D003000:Clonidine / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D054833:Isoindoles; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D011807:Quinolizines / Q000494:pharmacology; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects* / Q000378:metabolism; D015203:Reproducibility of Results; D014664:Vasodilation / Q000187:drug effects*; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; D007211:Indoles; D054833:Isoindoles; D011807:Quinolizines; D018341:Receptors, Adrenergic, alpha-2; C054290:L 657743; D010656:Phenylephrine; D015016:Yohimbine; D015740:Calcitonin Gene-Related Peptide; D003000:Clonidine; D000109:Acetylcholine; D002211:Capsaicin; C072125:BRL 44408