title: Pharmacological evidence that spinal α(2C)- and, to a lesser extent, α(2A)-adrenoceptors inhibit capsaicin-induced vasodilatation in the canine external carotid circulation.
abstract: During a migraine attack capsaicin-sensitive trigeminal sensory nerves release calcitonin gene-related peptide (CGRP), producing cranial vasodilatation and central nociception; hence, trigeminal inhibition may prevent this vasodilatation and abort migraine headache. This study investigated the role of spinal α₂-adrenoceptors and their subtypes (i.e. α(2A), α(2B) and/or α(2C)-adrenoceptors) in the inhibition of the canine external carotid vasodilator responses to capsaicin. Anaesthetized vagosympathectomized dogs were prepared to measure arterial blood pressure, heart rate and external carotid conductance. The thyroid artery was cannulated for one-min intracarotid infusions of capsaicin, α-CGRP and acetylcholine. A cannula was inserted intrathecally for spinal (C₁-C₃) administration of 2-amino-6-ethyl-4,5,7,8-tetrahydro-6H-oxazolo-[5,4-d]-azepin-dihydrochloride (B-HT 933; a selective α₂-adrenoceptor agonist) and/or the α₂-adrenoceptor antagonists rauwolscine (α(2A/2B/2C)), 2-[(4,5-dihydro-1H-imidazol-2-yl)methyl]-2,3-dihydro-1-methyl-1H-isoindole maleate (BRL44408; α(2A)), imiloxan (α(2B)) or acridin-9-yl-[4-(4-methylpiperazin-1-yl)-phenyl]amine (JP-1302; α(2C)). Infusions of capsaicin, α-CGRP and acetylcholine dose-dependently increased the external carotid conductance. Intrathecal B-HT 933 (1000 and 3100 μg) inhibited the vasodilator responses to capsaicin, but not those to α-CGRP or acetylcholine. This inhibition, abolished by rauwolscine (310 μg), was: (i) unaffected by 3,100 μg imiloxan; (ii) partially blocked by 310 μg of BRL44408 or 100 μg of JP-1302; and (iii) abolished by 1,000 μg of BRL44408 or 310 μg of JP-1302. Thus, intrathecal B-HT 933 inhibited the external carotid vasodilator responses to capsaicin. This response, mediated by spinal α₂-adrenoceptors unrelated to the α(2B)-adrenoceptor subtype, resembles the pharmacological profile of α(2C)-adrenoceptors and, to a lesser extent, α(2A)-adrenoceptors.
authors.affiliation: Departamento de Farmacobiología, Cinvestav-Coapa, Czda. de los Tenorios 235, Col. Granjas-Coapa, Deleg. Tlalpan, 14330 México D.F., Mexico. cvillalon@cinvestav.mx
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Villalón
authors.forename: Jorge
authors.initials: J
authors.lastname: Galicia-Carreón
authors.forename: Abimael
authors.initials: A
authors.lastname: González-Hernández
authors.forename: Bruno A
authors.initials: BA
authors.lastname: Marichal-Cancino
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Manrique-Maldonado
authors.forename: David
authors.initials: D
authors.lastname: Centurión
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D058669:Adrenergic alpha-2 Receptor Antagonists / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000627:therapeutic use; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002211:Capsaicin / Q000037:antagonists & inhibitors / Q000633:toxicity; D002342:Carotid Artery, External / Q000187:drug effects* / Q000502:physiology; D002574:Cervical Vertebrae; D004195:Disease Models, Animal; D004285:Dogs; D006439:Hemodynamics / Q000187:drug effects; D060186:Infusions, Spinal; D008297:Male; D008881:Migraine Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000378:metabolism; D018341:Receptors, Adrenergic, alpha-2 / Q000737:chemistry / Q000378:metabolism*; D012039:Regional Blood Flow / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D014665:Vasodilator Agents / Q000037:antagonists & inhibitors / Q000633:toxicity
chemical_list: D058669:Adrenergic alpha-2 Receptor Antagonists; D018712:Analgesics, Non-Narcotic; D020033:Protein Isoforms; D018341:Receptors, Adrenergic, alpha-2; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D015740:Calcitonin Gene-Related Peptide; D000109:Acetylcholine; D002211:Capsaicin