REGULATION OF HORMONE-RESPONSIVE ADENYLATE CYCLASE

激素反应性腺苷酸环化酶的调节

• 批准号: 3945231
• 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/3945231
• 关键词: adenylate cyclase; affinity chromatography; beta adrenergic agent; chorionic gonadotropin; drug interactions; hormone regulation /control mechanism; hypersensitivity desensitization; immunochemistry; isoproterenol; membrane fusion; phosphorylation; tissue /cell culture

1. Muscarinic receptors have been classified into M1- and M2- subtypes based on their affinity for the antagonist pirenzepine. We now show that both NG108-15 and SK-N-SH cells have M2 receptors. Yet, in the former cells, the receptors are coupled only to inhibition of adenylate cyclase; and in the latter cells, to stimulation of phosphoinositide breakdown. Thus, the same muscarinic receptor subtype can couple to two different signal transduction systems. 2. We have succeeded in solubilizing the D- 1 dopamine receptor from rat striatal membranes and reconstituting it into phospholipid vesicles. The receptor remains functional and couples to G proteins as measured by agonist high affinity state is increased over 6-fold from that in the original membranes. This may have important implications for the physiological state of the D-1 receptor in striatal membranes and its ability to mediate dopaminergic responses. 3. The hydrodynamic properties of the gonadotropin receptor from MLTC-1 cells has been determined. These cells contain gonadotropin receptors coupled to adenylate cyclase. Under nondenaturing conditions, the Mr of the receptor is 130 kDa compared to 80 kDa under denaturing conditions. Thus, the receptor may be composed of hormone-binding and non-binding subunits. Following desensitization of the cells by choriogonadotropin, the hydrodynamic properties of the receptor changes; the receptor binds less detergent and exhibits a more elongated frictional ratio but retains the same Mr. Thus, desensitization appears to involve a physical change in the gonadotropin receptor which may promote its uncoupling from adenylate cyclase.

1.M受体分为M_1和M_2。 亚型基于它们对拮抗剂哌仑西平的亲和力。 我们现在发现NG108-15和SK-N-SH细胞都有M2 感受器。然而，在前一个细胞中，受体是偶联的。 仅对腺苷环化酶有抑制作用；在后一种细胞中， 刺激肌醇磷脂分解。因此，相同的 M受体亚型可与两种不同的信号偶联 转导系统。2.我们成功地增溶了D- 1大鼠纹状体膜多巴胺受体和 将其重组为磷脂小泡。受体仍然存在 激动剂HIGH测定的功能性和偶联G蛋白 亲和力状态比原来增加了6倍以上。 膜。这可能会对 纹状体膜D-1受体的生理状态 其调节多巴胺能反应的能力。3. 人促性腺激素受体的流体力学性质 对MLTC-1细胞进行了鉴定。这些单元格包含 促性腺激素受体与腺苷环化酶偶联。在……下面 非变性条件下，受体的相对分子质量为130 kDa 与变性条件下的80 kDa相比。因此， 受体可分为激素结合型和非结合型 亚单位。在细胞脱敏后， 绒毛膜促性腺激素受体的流体力学特性 变化；受体结合的洗涤剂较少，表现出更多的 拉长的摩擦比但保持相同的MR， 脱敏似乎涉及到生理上的变化 促性腺激素受体可能促进其解偶联 腺苷环化酶。