Donaldson J, Kendall D A, Hill S J
Department of Physiology and Pharmacology, Medical School, Nottingham, England.
J Neurochem. 1990 May;54(5):1484-91. doi: 10.1111/j.1471-4159.1990.tb01195.x.
The effects of forskolin (1 microM) and EGTA (5 mM) on indirect cyclic AMP responses in slices of guinea-pig cerebral cortex were examined. Forskolin had little effect on the direct 2-chloroadenosine-stimulated cyclic AMP response. However, it completely abolished the glutamate-induced augmentation of this response. In contrast, forskolin had very little effect on the indirect cyclic AMP responses to noradrenaline, 5-hydroxytryptamine, and histamine. Conversely, rapid removal of extracellular calcium with EGTA 2 min before addition of the indirectly acting agent markedly reduced the augmentation responses produced by these latter agonists, but had little effect on the glutamate augmentation. When EGTA was added once a steady level of cyclic AMP had been achieved with the indirect agents, it was without effect on any of the responses. Thus, calcium appears to have a role in the early, but not the later, stages of the noradrenaline, 5-hydroxytryptamine, and histamine responses. A role for protein kinase C in the glutamate augmentation response was suggested, because forskolin inhibited the augmentation of the 2-chloroadenosine response produced by phorbol esters (which mimic the actions of diacylglycerol in activating protein kinase C). We conclude that there is more than one mechanism by which the augmentation of cyclic AMP responses can occur.
研究了福斯高林（1微摩尔）和乙二醇双（氨基乙基醚）四乙酸（EGTA，5毫摩尔）对豚鼠大脑皮层切片中间接环磷酸腺苷（cAMP）反应的影响。福斯高林对直接由2-氯腺苷刺激产生的cAMP反应影响很小。然而，它完全消除了谷氨酸诱导的该反应增强。相反，福斯高林对去甲肾上腺素、5-羟色胺和组胺引起的间接cAMP反应影响很小。相反，在添加间接作用剂前2分钟用EGTA快速去除细胞外钙，显著降低了后一种激动剂产生的增强反应，但对谷氨酸增强作用影响很小。当用间接作用剂使cAMP达到稳定水平后再添加EGTA时，它对任何反应均无影响。因此，钙似乎在去甲肾上腺素、5-羟色胺和组胺反应的早期而非后期发挥作用。提示蛋白激酶C在谷氨酸增强反应中起作用，因为福斯高林抑制了佛波酯（模拟二酰甘油激活蛋白激酶C的作用）产生的2-氯腺苷反应增强。我们得出结论，cAMP反应增强可能通过不止一种机制发生。
