阿片类药物依赖对腺苷酸环化酶的调节
Opiate-dependent modulation of adenylate cyclase.
作者信息
Sharma S K, Klee W A, Nirenberg M
出版信息
Proc Natl Acad Sci U S A. 1977 Aug;74(8):3365-9. doi: 10.1073/pnas.74.8.3365.
Abstract
Reactions mediated by the opiate receptors that inhibit adenylate cyclase (EC 4.6.1.1) are closely coupled to subsequent reactions that gradually increase adenylate cyclase activity of neuroblastoma X glioma NG108-15 hybrid cells. Opiate-treated cells have higher basal-, prostaglandin E1-, and 2-chloroadenosine-stimulated activities than do control cells. However, NaF or guanosine 5'-(beta, gamma-imido)triphosphate abolishes most of the differences in adenylate cyclase activity observed with homogenates from control and opiate-treated cells. Cycloheximide blocked some, but not all, of the opiate-dependent increase in adenylate cyclase activity. These results suggest that the opiate-dependent increase in adenylate cyclase is due to conversion of adenylate cyclase to a form with altered activity. Protein synthesis also is required for part of the opiate effect. We propose that activity of adenylate cyclase determines the rate of conversion of the enzyme from one form to the other and that opiates, by inhibiting adenylate cyclase, alter the relative abundance of low- and high-activity forms of the enzyme.
摘要
由抑制腺苷酸环化酶（EC 4.6.1.1）的阿片受体介导的反应与随后逐渐增加神经母细胞瘤X胶质瘤NG108 - 15杂交细胞腺苷酸环化酶活性的反应紧密相关。经阿片处理的细胞比对照细胞具有更高的基础活性、前列腺素E1刺激活性和2 - 氯腺苷刺激活性。然而，氟化钠或鸟苷5'-（β，γ-亚氨基）三磷酸消除了对照细胞和经阿片处理细胞匀浆中观察到的腺苷酸环化酶活性的大部分差异。环己酰亚胺阻断了部分但不是全部阿片依赖的腺苷酸环化酶活性增加。这些结果表明，阿片依赖的腺苷酸环化酶增加是由于腺苷酸环化酶转变为活性改变的形式。蛋白质合成对于部分阿片效应也是必需的。我们提出，腺苷酸环化酶的活性决定了该酶从一种形式转变为另一种形式的速率，并且阿片类药物通过抑制腺苷酸环化酶，改变了该酶低活性和高活性形式的相对丰度。
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