蛋白激酶C激活剂（佛波醇二丁酸酯）可减弱心房利钠因子刺激的平滑肌细胞中环鸟苷酸的积累。
An activator of protein kinase C (phorbol dibutyrate) attenuates atrial-natriuretic-factor-stimulated cyclic GMP accumulation in smooth-muscle cells.
作者信息
Nambi P, Whitman M, Aiyar N, Stassen F, Crooke S T
机构信息
Department of Molecular Pharmacology, Smith Kline & French Laboratories, Philadelphia, PA 19101.
出版信息
Biochem J. 1987 Jun 1;244(2):481-4. doi: 10.1042/bj2440481.
Abstract
Rat thoracic aortic smooth-muscle cells (A-10; A.T.C.C. CRL 1476) displays a high density of vasopressin and atrial-natriuretic-factor (ANF) receptors and a low density of beta-adrenergic receptors. ANF stimulates cGMP (cyclic GMP) accumulation in a time- and dose-dependent fashion. Pretreatment of these cells with phorbol dibutyrate (PDBu), a known activator of protein kinase C, attenuated ANF-stimulated cGMP accumulation without affecting basal cGMP concentrations. This effect was concentration-dependent and was observed as early as 2 min after treatment. 4 alpha-Phorbol 12, 13-didecanoate (alpha PDD), which does not activate protein kinase C, did not inhibit the cGMP accumulation. PDBu pretreatment did not affect the density and affinity of ANF receptors. These data suggest that PDBu, presumably via activation of protein kinase C, might stimulate phosphorylation of a key regulatory protein in the ANF/cGMP pathway.
摘要
大鼠胸主动脉平滑肌细胞（A-10；美国典型培养物保藏中心CRL 1476）显示出高浓度的血管加压素和心钠素（ANF）受体以及低浓度的β-肾上腺素能受体。ANF以时间和剂量依赖的方式刺激环磷酸鸟苷（cGMP）的积累。用佛波酯二丁酸酯（PDBu，一种已知的蛋白激酶C激活剂）预处理这些细胞，可减弱ANF刺激的cGMP积累，而不影响基础cGMP浓度。这种作用是浓度依赖性的，早在处理后2分钟就可观察到。不激活蛋白激酶C的4α-佛波醇12,13-二癸酸酯（αPDD）不抑制cGMP的积累。PDBu预处理不影响ANF受体的密度和亲和力。这些数据表明，PDBu可能通过激活蛋白激酶C，刺激ANF/cGMP途径中一种关键调节蛋白的磷酸化。
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