Blocking the L-type Ca²⁺ channel (Ca_v 1.2) is the key mechanism for the vascular relaxing effect of Pterodon spp. and its isolated diterpene methyl-6伪-acetoxy-7尾-hydroxyvouacapan-17尾-oate

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• 作者：Carolina de Fá ; tima Reis^a ; Daniela Medeiros Lobo de Andrade^a ; Bruno Junior Neves^c ; Leandra de Almeida Ribeiro Oliveira^b ; José ; Felippe Pinho^d ; Leidiane Pinha da Silva^d ; Jader Dos Santos Cruz^d ; Maria Teresa Freitas Bara^b ; Carolina Horta Andrade^c ; Matheus Lavorenti Rocha^a ; ^{matheusroch@yahoo.com.br" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Acetylcholine chloride (PubChem CID ; 6060) ; Bay K8644 (PubChem CID ; 2303) ; Cyclopiazonic acid (PubChem CID ; 54682463) ; ODQ ([1 ; 2 ; 4]oxadiazolo[4 ; 3-a]quinoxalin-1-one) (PubChem CID ; 1456) ; Phenylephrine hydrochloride (PubChem CID ; 5284443) ; Tetraethylammonium chloride (PubChem CID ; 5946) ; Verapamil hydrochloride (PubChem CID ; 62969)
• 刊名：Pharmacological Research
• 出版年：2015
• 出版时间：October 2015
• 年：2015
• 卷：100
• 期：Complete
• 页码：242-249
• 全文大小：1504 K

文摘

Pterodon spp. Vogel (Fabaceae), popularly known as “sucupira”, has ethnopharmacological application which is described as having antispasmodic and relaxant effects. Hence, it was hypothesized that sucupira oil-resin (SOR) could induce smooth muscle relaxation. So, this study investigated the mechanisms involved in the vasorelaxant effect of SOR and its isolated diterpene (methyl-6伪-acetoxy-7尾-hydroxyvouacapan-17尾-oate). Vascular reactivity experiments were performed using rat aortic rings (n = 5–8) with (E+) or without endothelium (E−) in an isolated bath organ. The SOR (0–56 渭g/mL) relaxed phenylephrine (E+: 86.7 ± 7.1%; E−: 92.3 ± 4.7%) and KCl contracted rings (E−: 97.1 ± 2.8%). In the same way, diterpene (0–48渭g/mL) also relaxed phenylephrine (E+: 94.5 ± 3.6%; E−: 92.2 ± 3.4%) and KCl contracted rings (E−: 99.7 ± 0.2%). The pre-incubation of arterial rings with cyclopiazonic acid (reticular Ca²⁺-ATPase inhibitor), tetraethylammonium (K+ channels blocker) or MDL-12,330A (adenylyl cyclesinhibitor) did not modify either SOR- or diterpeneinduced vasorelaxation. However, ODQ (guanylyl cyclase inhibitor) impaired only diterpene-induced vasorelaxation. SOR and diterpene significantly reduced CaCl₂-induced contraction stimulated by Bay K8644 (1 渭M), phenylephrine (0.1 渭M) or KCl solution (40 mM). Computational molecular docking studies demonstrated that the vasodilator effect of diterpene relies on blocking the Ca_v 1.2 channel, and patch clamp results showed that diterpene substantially decreased the ionic current through Ca_v 1.2 in freshly dissociated vascular smooth muscle cells. These findings suggest that SOR and its isolated diterpene induce endothelium-independent vascular relaxation by blocking the L-type Ca²⁺ channel (Ca_v 1.2).