CORTICOTROPIN-RELEASING HORMONE STIMULATION OF CA2+ ENTRY IN CORTICOTROPES IS PARTIALLY DEPENDENT ON PROTEIN-KINASE-A
CORTICOTROPIN-RELEASING HORMONE STIMULATION OF CA2+ ENTRY IN CORTICOTROPES IS PARTIALLY DEPENDENT ON PROTEIN-KINASE-A
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DOI：
10.1210/en.136.9.3925
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发表时间：
1995-09-01
期刊：
影响因子：
4.8
通讯作者：
RITCHIE, AK
中科院分区：
文献类型：
--
作者：
KURYSHEV, YA;CHILDS, GV;RITCHIE, AK
The modulation of membrane excitability and cytosolic Ca2+ levels by corticotropin-releasing hormone (CRH), (Bu)(2)cAMP (dBcAMP), and forskolin was examined in enriched populations of cultured rat anterior pituitary corticotropes. CRH (2 or 20 nM), dBcAMP (1 and 5 mM), and forskolin (10 mu M) caused a long lasting membrane depolarization accompanied by the onset of cell firing in quiescent cells or by increased firing frequency in spontaneously active cells. All three substances also increased cytosolic Ca2+ levels by increasing the frequency and amplitude of cytosolic Ca2+ transients. These results are consistent with a previous report on human corticotrope tumor cells demonstrating that CRH-induced action potentials lead to enhancement of Ca2+ uptake through voltage-dependent Ca2+ channels. Preincubation with (N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H-89), an inhibitor of cAMP-dependent protein kinase A, did not inhibit the CRH-induced depolarization, but attenuated the CRH-induced increase in action potential frequency. H-89 inhibited CRH-induced changes in cytosolic Ca2+ by 69% in spontaneously active cells and by 83% in quiescent cells. In contrast, H-89 completely abolished the effects of dBcAMP and forskolin on membrane potential and cytosolic Ca2+ levels. It is concluded that activation of protein kinase A mediates all of the response to dBcAMP and forskolin, but only a portion of the response to CRH. The portion of the response to CRH that is resistant to H-89 is mediated by a cAMP-independent mechanism.
