title: 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.
abstract: 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-(CB(1))/non-CB2 receptors. Here, we used the potent, selective CB(1) agonist arachidonylcyclopropylamide (ACPA) to elucidate the mechanism underlying vascular tone regulation. Immunohistochemistry and confocal microscopy revealed that CB(1) 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 CB(1) 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 (KCa1.1) (MaxiK; BKCa) 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(v)1.2). These results showed that ACPA activation of CB(1) in smooth muscle caused vasorelaxation of aortic rings through a mechanism involving the activation of K(Ca)1.1 and the inhibition of Ca(v)1.2.
authors.affiliation: Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, Av. 25 de Julio No. 965, Apdo. Postal No. 11, CP 28040 Colima, Colima, Mexico.
authors.forename: E
authors.initials: E
authors.lastname: Sánchez-Pastor
authors.affiliation: Instituto Tecnológico de Colima, Avenida Tecnológico No. 1, CP 28976 Villa de Álvarez, Colima, Mexico.
authors.forename: F
authors.initials: F
authors.lastname: Andrade
authors.affiliation: Instituto Tecnológico de Colima, Avenida Tecnológico No. 1, CP 28976 Villa de Álvarez, Colima, Mexico.
authors.forename: J M
authors.initials: JM
authors.lastname: Sánchez-Pastor
authors.affiliation: Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, Av. 25 de Julio No. 965, Apdo. Postal No. 11, CP 28040 Colima, Colima, Mexico.
authors.forename: A
authors.initials: A
authors.lastname: Elizalde
authors.affiliation: Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, Av. 25 de Julio No. 965, Apdo. Postal No. 11, CP 28040 Colima, Colima, Mexico. Electronic address: huertam@ucol.mx.
authors.forename: M
authors.initials: M
authors.lastname: Huerta
authors.affiliation: Departamento de Ciencias Químico Biológicas, División de Ciencias e Ingenierías, Unidad Regional Sur, Campus Navojoa, Universidad de Sonora, Lázaro Cárdenas No. 100, Colonia Francisco Villa, CP 85800 Navojoa, Sonora, Mexico.
authors.forename: A
authors.initials: A
authors.lastname: Virgen-Ortiz
authors.affiliation: Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, Av. 25 de Julio No. 965, Apdo. Postal No. 11, CP 28040 Colima, Colima, Mexico.
authors.forename: X
authors.initials: X
authors.lastname: Trujillo
authors.affiliation: Facultad de Medicina, Universidad de Colima, Av. Universidad 333, Las Víboras, 28040 Colima, Colima, Mexico.
authors.forename: A
authors.initials: A
authors.lastname: Rodríguez-Hernández
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D001095:Arachidonic Acids / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000819:agonists / Q000378:metabolism*; D008297:Male; D009924:Organ Culture Techniques; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000378:metabolism*; D050916:TRPV Cation Channels / Q000819:agonists / Q000378:metabolism*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
chemical_list: D001095:Arachidonic Acids; D020746:Calcium Channels, L-Type; C494842:Kcnma1 protein, rat; C419385:L-type calcium channel alpha(1C); D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D043884:Receptor, Cannabinoid, CB1; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; C119324:arachidonylcyclopropylamide; D002118:Calcium
keywords: ACPA; Aorta; CB(1) receptors; Ca(2+) channels; Cannabinoids; MaxiK channels