Jaiswal R K
Department of Brain and Vascular Research, Cleveland Clinic Research Institute, OH 44195.
Biochem Biophys Res Commun. 1992 Jan 15;182(1):395-402. doi: 10.1016/s0006-291x(05)80158-5.
Preincubation of rat thoracic aortic smooth muscle cells with endothelin inhibits the atrial natriuretic factor (ANF)-induced cGMP accumulation in these cells in a concentration dependent manner. The maximal inhibition of 64% was afforded by 1 x 10(-6) M endothelin and the half maximal inhibition (IC50) was achieved with 1 x 10(-9) M endothelin. Endothelin (1 x 10(-6) M) also increased the plasma membrane bound protein kinase C (PKC) activity by 4 fold. Hormone-dependent increase in PKC activity was limited to plasma membranes only and some decrease in cytosolic PKC activity was observed. However, phorbol 12-myristate 13-acetate (PMA) (1 x 10(-6)M) provoked a total loss of cytosolic PKC activity and a net gain in membranous PKC activity indicative of the translocation of the enzyme. Pretreatment of these cells with H-7, a PKC inhibitor, released the endothelin and PMA-mediated attenuation of ANF-stimulated cGMP formation. These results suggest that PKC is involved in the regulation of ANF-induced cGMP accumulation and that the vasoconstrictor activity of endothelin might involve inhibition of the vasorelaxant activity of ANF through the inhibition of cGMP accumulation in smooth muscle cells (SMCs) of the rat aorta.
用内皮素对大鼠胸主动脉平滑肌细胞进行预孵育，可浓度依赖性地抑制这些细胞中由心房利钠因子（ANF）诱导的环鸟苷酸（cGMP）积累。1×10⁻⁶ M内皮素可产生64%的最大抑制作用，而1×10⁻⁹ M内皮素可实现半数最大抑制（IC50）。内皮素（1×10⁻⁶ M）还可使质膜结合蛋白激酶C（PKC）的活性增加4倍。PKC活性的激素依赖性增加仅局限于质膜，且观察到胞质PKC活性有所下降。然而，佛波醇12 - 肉豆蔻酸酯13 - 乙酸酯（PMA）（1×10⁻⁶M）可导致胞质PKC活性完全丧失，质膜PKC活性净增加，这表明该酶发生了易位。用PKC抑制剂H - 7对这些细胞进行预处理，可消除内皮素和PMA介导的对ANF刺激的cGMP形成的减弱作用。这些结果表明，PKC参与了对ANF诱导的cGMP积累的调节，并且内皮素的血管收缩活性可能通过抑制大鼠主动脉平滑肌细胞（SMC）中的cGMP积累来抑制ANF的血管舒张活性。
