Jaiswal N, Jaiswal R K, Malik K U
Department of Pharmacology, University of Tennessee, Memphis 38163.
Mol Pharmacol. 1991 Jul;40(1):101-6.
The purpose of the present study was to determine the subtype of muscarinic receptor involved in the action of cholinergic stimuli on synthesis of prostacyclin, measured as immunoreactive 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), and cGMP in bovine aortic endothelial and rabbit vascular smooth muscle cells. Acetylcholine and arecaidine propargyl ester, a selective M2 agonist, produced a dose-dependent increase in 6-keto-PGF1 alpha output and cGMP formation in confluent endothelial cells but not in confluent vascular smooth muscle cells. McN-A-343, a selective M1 agonist, failed to alter basal 6-keto-PGF1 alpha or cGMP synthesis. Acetylcholine- and arecaidine propargyl ester-induced 6-keto-PGF1 alpha synthesis and cGMP formation in endothelial cells were attenuated by atropine, AF-DX 116 (M2 antagonist), and hexahydrosiladifenidol (M3 antagonist) but not by pirenzepine (M1 antagonist). The cyclooxygenase inhibitor indomethacin abolished 6-keto-PGF1 alpha synthesis but not the increase in cGMP formation elicited by the cholinergic stimuli. Our data suggest that the effect of cholinergic stimuli to enhance prostacyclin and cGMP synthesis is mediated via activation of M2 and M3 receptors located on endothelial cells and that the increase in cGMP production is independent of prostaglandins.
本研究的目的是确定参与胆碱能刺激对前列环素合成作用的毒蕈碱受体亚型，以前列环素合成通过免疫反应性6-酮-前列腺素F1α（6-酮-PGF1α）来衡量，同时研究其对牛主动脉内皮细胞和兔血管平滑肌细胞中环鸟苷酸（cGMP）的影响。乙酰胆碱和一种选择性M2激动剂——炔丙基阿瑞吡啶，可使融合的内皮细胞中6-酮-PGF1α产量和cGMP生成呈剂量依赖性增加，但对融合的血管平滑肌细胞无此作用。选择性M1激动剂McN-A-343未能改变基础6-酮-PGF1α或cGMP的合成。阿托品、AF-DX 116（M2拮抗剂）和六甲硅烷二苯哌啶（M3拮抗剂）可减弱乙酰胆碱和炔丙基阿瑞吡啶诱导的内皮细胞中6-酮-PGF1α合成和cGMP生成，但哌仑西平（M1拮抗剂）则无此作用。环氧合酶抑制剂吲哚美辛可消除6-酮-PGF1α合成，但不能消除胆碱能刺激引起的cGMP生成增加。我们的数据表明，胆碱能刺激增强前列环素和cGMP合成的作用是通过激活内皮细胞上的M2和M3受体介导的，且cGMP生成的增加与前列腺素无关。
