Pharmacological Evidence for Involvement of Phospholipase D, Protein Kinase C, and Sodium-Calcium Exchanger in α-Adrenoceptor-Mediated Negative Inotropy in Adult Mouse Ventricle

[摘要] References(44)Cited-By(7)The intracellular signalling pathway for α-adrenoceptor-mediated negative inotropy was studied pharmacologically in isolated adult mouse ventricle. The negative inotropy was inhibited by GF-109203X, a nonselective protein kinase C inhibitor. Phorbol 12-myristate 13-acetate also produced sustained negative inotropy, which was inhibited by KB-R7943, a Na+/Ca2+ exchanger inhibitor. The α-adrenoceptor-mediated negative inotropy was augmented by RHC-80267, a diacylglycerol lipase inhibitor, but was inhibited either by C2-ceramide, a phospholipase D inhibitor, and high concentration of propranolol (50 μM), which inhibits phosphatidate phosphohydrolase. The inotropy was not affected by U-73122, a phospholipase C inhibitor. Lavendustin-A, a tyrosine kinase inhibitor, also inhibited the negative inotropy. These findings suggest that α-adrenoceptor-mediated negative inotropy in adult mouse ventricle is mediated by activation of tyrosine kinase, the phospholipase D-phosphatidate phosphohydrolase pathway, and protein kinase C.

[学科分类] 药学

[关键词] α-adrenoceptor;inotropy;phospholipase D;protein kinase C