Cannabinoid receptor type 1 activation by arachidonylcyclopropylamide in rat aortic rings causes vasorelaxation involving calcium-activated potassium channel subunit alpha-1 and calcium channel, voltage-dependent, L type, alpha 1C subunit

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• 作者：E. Sá ; nchez-Pastor^a ; F. Andrade^b ; J.M. Sá ; nchez-Pastor^b ; A. Elizalde^a ; M. Huerta^a ; ^{huertam@ucol.mx" class="auth_mail} ; A. Virgen-Ortiz^c ; X. Trujillo^a ; A. Rodrí ; guez-Herná ; ndez^d
• 关键词：CB1 receptors ; Cannabinoids ; ACPA ; Aorta ; MaxiK channels ; Ca2+ channels
• 刊名：European Journal of Pharmacology
• 出版年：15 April, 2014
• 年：2014
• 卷：729
• 期：Complete
• 页码：100-106
• 全文大小：2075 K

文摘

Cannabinoids are key regulators of vascular tone, some of the mechanisms involved include the activation of cannabinoid receptor types 1 and 2 (CB); the transient receptor potential cation channel, subfamily V, member 1 (TRPV1); and non-(CB₁)/non-CB₂ receptors. Here, we used the potent, selective CB₁ agonist arachidonylcyclopropylamide (ACPA) to elucidate the mechanism underlying vascular tone regulation. Immunohistochemistry and confocal microscopy revealed that CB₁ was expressed in smooth muscle and endothelial cells in rat aorta. We performed isometric tension recordings in aortic rings that had been pre-contracted with phenylephrine. In these conditions, ACPA caused vasorelaxation in an endothelium-independent manner. To confirm that the effect of ACPA was mediated by CB₁ receptor, we repeated the experiment after blocking these receptors with a selective antagonist, AM281. In these conditions, ACPA did not cause vasorelaxation. We explored the role of K⁺ channels in the effect of ACPA by applying high-K⁺ solution to induce contraction in aortic rings. In these conditions, the ACPA-induced vasorelaxation was about half that observed with phenylephrine-induced contraction. Thus, K⁺ channels were involved in the ACPA effect. Furthermore, the vasorelaxation effect was similarly reduced when we specifically blocked calcium-activated potassium channel subunit alpha-1 (K_Ca1.1) (MaxiK; BK_Ca) prior to adding ACPA. Finally, ACPA-induced vasorelaxation was also diminished when we specifically blocked the calcium channel, voltage-dependent, L type, alpha 1C subunit (Ca_v1.2). These results showed that ACPA activation of CB₁ in smooth muscle caused vasorelaxation of aortic rings through a mechanism involving the activation of K_Ca1.1 and the inhibition of Ca_v1.2.