Davis J R, Sheppard M C
Department of Endocrinology, Queen Elizabeth Hospital, Edgbaston, Birmingham, U.K.
Mol Cell Endocrinol. 1987 Dec;54(2-3):197-201. doi: 10.1016/0303-7207(87)90157-2.
We have investigated the interactions of intracellular messenger systems which may regulate thyrotrophin (TSH) release in primary cultures of rat anterior pituitary cells. Calcium ionophore A23187 was used to raise intracellular free calcium, the phorbol ester 12-O-tetradecanoyl phorbol-13-acetate (TPA) to activate protein kinase C, and forskolin to activate adenylate cyclase. Each of these agents stimulated TSH secretion in a dose-dependent manner, but the effect of forskolin was delayed for at least 6 h. The combined effects of A23187 and TPA on TSH secretion were simply additive, but forskolin synergistically enhanced the effect of A23187 and 55 mM potassium, but not that of TPA. Co-incubation of cells with 1 microM A23187 caused parallel upward shift of the TPA dose-response curve, and the further addition of 10 microM forskolin led to further upward shift. These results suggest that calcium mobilization and adenylate cyclase activation may interact synergistically to modulate TSH secretion. Raised cellular cyclic AMP content may amplify further the TSH release stimulated by the combination of protein kinase C activation and raised intracellular free calcium.
我们研究了细胞内信使系统之间的相互作用，这些系统可能调节大鼠垂体前叶细胞原代培养物中促甲状腺激素（TSH）的释放。钙离子载体A23187用于提高细胞内游离钙水平，佛波酯12-O-十四酰佛波醇-13-乙酸酯（TPA）用于激活蛋白激酶C，福斯高林用于激活腺苷酸环化酶。这些试剂中的每一种都以剂量依赖的方式刺激TSH分泌，但福斯高林的作用延迟至少6小时。A23187和TPA对TSH分泌的联合作用只是简单相加，但福斯高林协同增强了A23187和55 mM钾的作用，而不是TPA的作用。将细胞与1 microM A23187共同孵育导致TPA剂量反应曲线平行上移，进一步添加10 microM福斯高林导致进一步上移。这些结果表明，钙动员和腺苷酸环化酶激活可能协同相互作用以调节TSH分泌。细胞内环状AMP含量的升高可能进一步放大由蛋白激酶C激活和细胞内游离钙升高的组合刺激的TSH释放。
