Clonidine inhibits the canine external carotid vasodilatation to capsaicin by α2A/2C-adrenoceptors
European Journal of Pharmacology , Volume 543 - Issue 1-3 p. 68- 76
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 α2-adrenoceptor agonist, clonidine, on the external carotid vasodilator responses to capsaicin, α-CGRP and acetylcholine. 1-min intracarotid infusions of capsaicin (10, 18, 30 and 56 μg/min), α-CGRP (0.1, 0.3, 1 and 3 μg/min) and acetylcholine (0.01, 0.03, 0.1 and 0.3 μg/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 α-CGRP or acetylcholine, were partially inhibited after clonidine (total dose: 24.4 μg/kg, i.v.); in contrast, equivalent volumes of saline did not affect the responses to capsaicin, α-CGRP or acetylcholine. The inhibitory responses to clonidine were antagonized by i.v. administration of the α2-adrenoceptor antagonists rauwolscine (α2A/2B/2C; 300 μg/kg), BRL44408 (α2A; 1000 μg/kg) or MK912 (α2C; 100 and 300 μg/kg), but not by imiloxan (α2B; 1000 μg/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 α2A-adrenoceptors and, to a much lesser extent, by α2C-adrenoceptors.
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Jiménez-Mena, L.R, Gupta, S, Muñoz-Islas, E, Lozano-Cuenca, J, Sánchez-López, A, Centurion, D, … Villalón, C.M. (2006). Clonidine inhibits the canine external carotid vasodilatation to capsaicin by α2A/2C-adrenoceptors. European Journal of Pharmacology, 543(1-3), 68–76. doi:10.1016/j.ejphar.2006.05.041