Spinal sumatriptan inhibits capsaicin-induced canine external carotid vasodilatation via 5-HT1B rather than 5-HT1D receptors
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- 作者：Enriqueta Muñ ; oz-Islas ; Jair Lozano-Cuenca ; Abimael Gonzá ; lez-Herná ; ndez ; Martha B. Ramí ; rez-Rosas ; Araceli Sá ; nchez-Ló ; pez ; David Centurió ; n ; Antoinette MaassenVanDenBrink
- 关键词：BRL15572 ; Capsaicin ; α ; -CGRP ; External carotid vasodilatation ; Migraine ; SB224289 ; Sumatriptan
- 刊名：European Journal of Pharmacology
- 出版年：2009
- 出版时间：1 August 2009
- 年：2009
- 卷：615
- 期：1-3
- 页码：133-138
- 全文大小：588 K
文摘
Migraine is a neurovascular disorder associated with trigeminal activation, vasodilatation and trigeminal release of calcitonin gene-related peptide (CGRP). The antimigraine properties of triptans may be due to: i) vasoconstriction of the carotid arterial bed via 5-HT1B receptors; and ii) inhibition of CGRP release from trigeminal nerves, via 5-HT1B/1D receptors. This study investigated the effects of intrathecally administered sumatriptan (a 5-HT1B/1D receptor agonist) and PNU-142633 (a 5-HT1D receptor agonist) on the canine external carotid vasodilator responses to capsaicin, α-CGRP and acetylcholine. For this purpose, 42 mongrel dogs were anaesthetised with sodium pentobarbitone and, subsequently, vagosympathectomized. The animals were prepared to measure arterial blood pressure, heart rate and external carotid blood flow; the thyroid artery was cannulated for infusion of agonists. 1-min intracarotid (i.c.) continuous infusions of capsaicin, α-CGRP and acetylcholine produced dose-dependent increases in external carotid blood flow without affecting arterial blood pressure or heart rate. These vasodilator responses remained unaffected after intrathecal (i.t.) administration of physiological saline (0.5 ml) or PNU-142633 (300–1000 μg); in contrast, i.t. sumatriptan (300–1000 μg) significantly inhibited the vasodilator responses to capsaicin, but not those to α-CGRP or acetylcholine. Furthermore, i.t. administration of SB224289 (a 5-HT1B receptor antagonist), but not of BRL15572 (a 5-HT1D receptor antagonist), abolished the above inhibition by sumatriptan. These results suggest that sumatriptan-induced inhibition of the external carotid vasodilatation to capsaicin involves a central mechanism mainly mediated by 5-HT1B receptors.