An activator of protein kinase C (phorbol dibutyrate) attenuates atrial-natriuretic-factor-stimulated cyclic GMP accumulation in smooth-muscle cells.
An activator of protein kinase C (phorbol dibutyrate) attenuates atrial-natriuretic-factor-stimulated cyclic GMP accumulation in smooth-muscle cells.
复制标题
蛋白激酶 C（佛波二丁酸）激活剂可减弱心房钠尿因子刺激的平滑肌细胞中的环 GMP 积累。
作者：
P. Nambi;M. Whitman;N. Aiyar;F. Stassen;S. Crooke
大鼠胸主动脉平滑肌细胞（A-10；A.T.C.C. CRL 1476）表现出高密度的加压素和心房钠尿因子 (ANF) 受体以及低密度的 β-肾上腺素能受体。 ANF 以时间和剂量依赖性方式刺激 cGMP（环状 GMP）积累。用佛波二丁酸 (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。这种效应是浓度依赖性的，并且最早在治疗后 2 分钟就可以观察到。 4 α-佛波醇 12, 13-二癸酸酯 (α PDD) 不会激活蛋白激酶 C，也不会抑制 cGMP 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 可能通过蛋白激酶 C 的激活，可能刺激 ANF/cGMP 途径中关键调节蛋白的磷酸化。
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.