The endothelial component of cannabinoid-induced relaxation in rabbit mesenteric artery depends on gap junctional communication

作     者：Chaytor, AT Martin, PEM Evans, WH Randall, MD Griffith, TM 

作者机构：Univ Wales Coll Med Dept Diagnost Radiol Cardiovasc Sci Res Grp Cardiff CF4 4XN S Glam Wales Univ Wales Coll Med Dept Biochem Med Cardiovasc Sci Res Grp Cardiff CF4 4XN S Glam Wales Univ Nottingham Sch Med Sch Biomed Sci Queens Med Ctr Nottingham NG7 2UH England 

出 版 物：《JOURNAL OF PHYSIOLOGY-LONDON》 (生理学杂志)

年 卷 期：1999年第520卷第2期

页      面：539-550页

核心收录：

学科分类：0710[理学-生物学] 1001[医学-基础医学(可授医学、理学学位)] 07[理学] 071003[理学-生理学] 

主　　题：乙酰胆碱/药理学 花生四烯酸类/药理学 苯呋喃类/药理学 COS细胞 大麻酚类/拮抗剂和抑制剂 大麻酚类/药理学 内源性大麻酚类 缝隙接合部/药物作用 缝隙接合部/生理学 甘草次酸/类似物和衍生物 甘草次酸/药理学 吲哚美辛/药理学 异喹啉类 肠系膜上动脉/药物作用 肠系膜上动脉/代谢 肌松弛 肌 平滑 血管/药物作用 肌 平滑 血管/代谢 NG-硝基精氨酸甲酯/药理学 苯福林/药理学 哌啶类/药理学 多不饱和脂肪酸酰胺类 吡唑类/药理学 受体 大麻酚 受体 药物/拮抗剂和抑制剂 受体 药物/代谢 动物 男(雄)性 兔 

摘      要：1. We have shown that the endocannabinoid anandamide and its stable analogue methanandamide relax rings of rabbit superior mesenteric artery through endothelium-dependent and -independent mechanisms that are unaffected by blockade of NO synthase and cyclooxygenase. 2. The endothelium-dependent component of the responses was attenuated by the gap junction inhibitor 18 alpha-glycyrrhetinic acid (18 alpha-GA;50 mu m), and a synthetic connexin-mimetic peptide homologous to the extracellular Gap 27 sequence of connexin 43 ((43)Gap 27, SRPTEKTIFII;300 mu M) By contrast, the corresponding connexin 40 peptide ((40)Gap 27, SRPTEKNVFIV) was inactive. 3. The cannabinoid CB1 receptor antagonist SR141716A (10 mu M) also attenuated endothelium-dependent relaxations but this inhibition nas not observed with the CB, receptor antagonist LY320135 (10 mu M) Furthermore, SR141716A mimicked the effects of (43)Gap 27 peptide in blocking Lucifer Yellow dye transfer between coupled COS-7 cells (a monkey fibroblast cell line), whereas LY320135 was without effect, thus suggesting that the action of SR141716A was directly attributable to effects on gap junctions. 4. The endothelium-dependent component of cannabinoid-induced relaxation was also attenuated by AM404 (10 mu M), an inhibitor of the high-affinity anandamide transporter, which was without effect on dye transfer. 5. Taken together, the findings suggest that cannabinoids derived from arachidonic acid gain access to the endothelial cytosol via a transporter mechanism and subsequently stimulate relaxation by promoting diffusion of an endothelium-derived hyperpolarizing factor to adjacent smooth muscle cells via gap junctions. 6. Relaxations of endothelium-denuded preparations to anandamide and methanandamide were unaffected by (43)Gap 27 peptide, 18 alpha-GA, SR141716A, AM404 and indomethacin and their genesis remains to be established.