Opiate-dependent modulation of adenylate cyclase.

Abstract
Reactions mediated by opiate receptors that inhibit adenylate cyclase (EC 4.6.1.1) are closely coupled to subsequent reactions that gradually increase adenylate cyclase activity of [mouse] neuroblastoma .times. glioma NG108-15 hybrid cells. Opiate-treated cells have higher basal-, prostaglandin E1- and 2-chloroadenosine-stimulated activities than do control cells. NaF or guanosine 5''-(.beta.,.gamma.-imido)triphosphate abolishes most of the difference 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. The opiate-dependent increase in adenylate cyclase may be due to conversion of adenylate cyclase to a form with altered activity. Protein synthesis is required for part of the opiate effect. Adenylate cyclase activity probably determines the rate of enzyme conversion from 1 form to other other, and opiates, by inhibiting adenylate cyclase, alter the relative abundance of low- and high-activity forms of the enzyme.