REGULATION OF HORMONE-RESPONSIVE ADENYLATE CYCLASE

激素反应性腺苷酸环化酶的调节

• 批准号: 3922526
• 负责人: P H FISHMAN
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3922526
• 关键词: Leydig cells; adenylate cyclase; affinity chromatography; beta adrenergic agent; calcium metabolism; calmodulin; chorionic gonadotropin; cyclic AMP; dopamine receptor; hormone receptor; hormone regulation /control mechanism; messenger RNA; muscarinic receptor; neoplastic cell; neuroblastoma; neurohypophyseal hormone; neuropeptides; oxytocin; phorbols; phosphatidylinositols; protein kinase C; vasoconstrictors; vasopressins

Stimulation of muscarinic receptors in SK-N-SH human neuroblastoma cells leads to both phosphoinositide breakdown and stimulation of adenylate cyclase. This novel response is due to cross-talk between these two major signal transduction systems and appears to be mediated by a calcium/calmodulin-dependent process. As SK-N-SH cells express the m3 subtype muscarinic receptor, cross-talk may involve this receptor subtype. We have succeeded in solubilizing the D-1 dopamine receptor from both rat and bovine striatal membranes and are using a novel affinity chromatography procedure to purify it. We have shown that neuropeptide Y (NPY) inhabits adenylate cyclase in SK-N-MC human neuroblastoma cells. As inhibition is blocked by treating the cells with pertussis toxin, the NPY receptors are coupled through the inhibitory regulatory protein GI to adenylate cyclase. The availability of a continuous cell line will accelerate progress on characterizing NPY receptors and the mode of action of this important vasoconstrictor. Both human choriogonadotropin (hCG) and phorbol esters causes desensitization of the hCG receptor-coupled adenylate cyclase in murine Leydig tumor (MLTC-1) cells. Whereas phorbol esters activate protein kinase C, hCG does not. Thus, distinct mechanisms of desensitization appear to be involved. This has been confirmed in a cell-free system; hCG, but not phorbol esters cause desensitization of the membranes. Addition of purified protein kinase C to the membranes, however, does cause desensitization. MLTC-1 cells express messenger RNA for oxytocin and vasopressin. Stimulation of the cells with hCG leads to a decrease in their mRNA levels. This regulation is medicated by cyclic AMP as it can be an important source for these neurohypophysial hormones and their synthesis may be controlled by gonadotropins.

人神经母细胞瘤SK-N-SH中M受体的激活 细胞导致磷酸肌醇分解和刺激 腺苷酸环化酶 这种新颖的反应是由于串扰 在这两个主要的信号转导系统之间， 由钙/钙调蛋白依赖性过程介导。 作为SK-N-SH 细胞表达M3亚型毒蕈碱受体，串扰可能 涉及这种受体亚型。 我们成功地溶解了 大鼠和牛纹状体D-1多巴胺受体 膜，并使用一种新的亲和层析程序 我们已经证明，神经肽Y（NPY）存在于 腺苷酸环化酶在SK-N-MC人神经母细胞瘤细胞中的表达。 作为 通过用百日咳毒素处理细胞来阻断抑制作用， 神经肽Y受体通过抑制性调节性 蛋白GI转化为腺苷酸环化酶。 连续的可用性 细胞系将加速表征NPY受体的进展 以及这种重要的血管收缩剂的作用方式。 两 人绒毛膜促性腺激素（hCG）和佛波酯导致 hCG受体偶联腺苷酸环化酶的脱敏作用 小鼠睾丸间质肿瘤（MLTC-1）细胞。 而佛波醇酯 激活蛋白激酶C，而hCG不激活。 因此，不同的机制 似乎与脱敏有关。 证实了这一点 在无细胞系统中; hCG，而不是佛波醇酯引起 膜的脱敏。 添加纯化蛋白 然而，激酶C对膜的作用确实会导致脱敏。 MLTC-1细胞表达催产素和加压素的信使RNA。 用hCG刺激细胞导致其mRNA的减少， 程度. 这种调节是由环磷酸腺苷，因为它可以 这些神经垂体激素的重要来源， 合成可由促性腺激素控制。