Crook R B, Yabu J M
Department of Ophthalmology, University of California, San Francisco 94143.
Biochem Biophys Res Commun. 1992 Oct 30;188(2):662-70. doi: 10.1016/0006-291x(92)91107-2.
Calcitonin gene-related peptides I and II (CGRP I and II) were found to stimulate cAMP levels by approximately 4-6 fold in human nonpigmented ciliary epithelial cells with half-maximal effective concentrations of 20 x 10(-10) and 3 x 10(-10) M, respectively. Prior exposure of cells to 6 x 10(-7) M phorbol 12-myristate, 13-acetate for 15 min resulted in a 40-50% inhibition of CGRP II-dependent cAMP stimulation. Phorbol didecanoate and dioctanoylglycerol also effectively inhibited, whereas 4 alpha phorbol didecanoate, an ineffective activator of protein kinase C, had no effect. Staurosporine, a protein kinase C inhibitor, blocked the inhibition of cAMP formation by phorbol esters. cAMP stimulation by forskolin or cholera toxin was not inhibited by phorbol esters, suggesting that neither a Gs protein nor adenylyl cyclase is the site of inhibition by protein kinase C. These data therefore suggest that CGRP receptors are required for inhibition of adenylate cyclase by protein kinase C.
降钙素基因相关肽I和II（CGRP I和II）在人无色素睫状上皮细胞中可使环磷酸腺苷（cAMP）水平升高约4 - 6倍，其半数有效浓度分别为20×10⁻¹⁰和3×10⁻¹⁰ M。细胞预先暴露于6×10⁻⁷ M佛波醇12 - 肉豆蔻酸酯13 - 乙酸酯15分钟，会导致CGRP II依赖性cAMP刺激受到40 - 50%的抑制。佛波醇十二烷酸酯和二辛酰甘油也有有效抑制作用，而4α佛波醇十二烷酸酯（一种无效的蛋白激酶C激活剂）则无作用。蛋白激酶C抑制剂星形孢菌素可阻断佛波醇酯对cAMP形成的抑制作用。佛波醇酯不会抑制福斯高林或霍乱毒素对cAMP的刺激，这表明Gs蛋白和腺苷酸环化酶都不是蛋白激酶C的抑制位点。因此，这些数据表明蛋白激酶C抑制腺苷酸环化酶需要CGRP受体。
