Short-term plasticity of cyclic adenosine 3′,5′-monophosphate signaling in anterior pituitary corticotrope cells:: The role of adenylyl cyclase isotypes
Short-term plasticity of cyclic adenosine 3′,5′-monophosphate signaling in anterior pituitary corticotrope cells:: The role of adenylyl cyclase isotypes
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DOI：
10.1210/me.2002-0369
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发表时间：
2003-04-01
影响因子：
--
通讯作者：
Simpson, J
中科院分区：
文献类型：
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作者：
Antoni, FA;Sosunov, AA;Simpson, J
垂体前叶促肾上腺皮质激素对下丘脑神经肽和肾上腺皮质激素有广泛的反应。研究了cAMP信号系统的可塑性是这种适应性多功能性的基础的假设。在分散的大鼠垂体前叶细胞中，细胞内钙池的耗竭与thapsigargin结合ryanodine或咖啡因增强促肾上腺皮质激素释放因子（CRF）诱发的cAMP反应的4倍，而单独减少的Ca 2+进入没有影响。CRF诱导的cAMP被精氨酸加压素（AVP）或佛波醇二丁酸酯放大15倍。在环核苷酸磷酸二酯酶和佛波醇二丁酸酯的抑制剂的存在下，消耗的Ca 2+商店CRF诱导的cAMP积累没有进一步的影响。Ca 2+抑制腺苷酸环化酶（ACs）VI和IX，和蛋白激酶C刺激的ACs II和VII的mRNA的腺垂体表达被证明。ACIX检测促皮质激素的免疫细胞化学，而ACII和ACVI不存在。数据显示CRF诱导的cAMP水平的负反馈调节钙离子来自兰尼碱受体操作的细胞内商店。AVP对蛋白激酶C的刺激增强了非钙依赖性cAMP的合成，从而改变了细胞内钙反馈的特征。这表明AVP对促皮质细胞内Ca ~（2+）反馈的调节是其生理调控的重要组成部分。
Anterior pituitary corticotropes show a wide repertory of responses to hypothalamic neuropeptides and adrenal corticosteroids. The hypothesis that plasticity of the cAMP signaling system underlies this adaptive versatility was investigated. In dispersed rat anterior pituitary cells, depletion of intracellular Ca2+ stores with thapsigargin combined with ryanodine or caffeine enhanced the corticotropin releasing-factor (CRF)-evoked cAMP response by 4-fold, whereas reduction of Ca2+ entry alone had no effect. CRF-induced cAMP was amplified 15-fold by arginine-vasopressin (AVP) or phorbol-dibutyrate ester. In the presence of inhibitors of cyclic nucleotide phosphodiesterases and phorbol-dibutyrate ester, the depletion of Ca2+ stores had no further effect on CRF-induced cAMP accumulation. Adenohypophysial expression of mRNAs for the Ca2+-inhibited adenylyl cyclases (ACs) VI and IX, and the protein kinase C-stimulated ACs II and VII was demonstrated. ACIX was detected in corticotropes by immunocytochemistry, whereas ACII and ACVI were not present. The data show negative feedback regulation of CRF-induced cAMP levels by Ca2+ derived from ryanodine receptor-operated intracellular stores. Stimulation of protein kinase C by AVP enhances Ca2+-independent cAMP synthesis, thus changing the characteristics of intracellular Ca2+ feedback. It is proposed that the modulation of intracellular Ca2+ feedback in corticotropes by AVP is an important element of physiological control.