Modulation of sodium-sensitive GTPase by partial opiate agonists. An explanation for the dual requirement for Na+ and GTP in inhibitory regulation of adenylate cyclase.
Opiates and opioid peptides inhibit adenylate cyclase and stimulate specific low Km GTPase activity in membranes from neuroblastoma x glioma NG108-15 hybrid cells. The effects of opiate agonists on both enzymes are mediated by high affinity stereospecific receptors and require Mg2+, GTP, and Na+. In the presence of Mg2+, Na+ inhibits basal GTPase activity; opiates stimulate GTP hydrolysis by antagonizing the Na+-induced inhibition. Activation of GTPase leads, in turn, to inactivation of GTP-stimulated adenylate cyclase activity. The intrinsic activities (or efficacies) of a series of opiates are identical for stimulation of GTPase and inhibition of adenylate cyclase. These results provide a mechanism for the dual requirement for Na+ and GTP in the inhibitory coupling of opiate receptors to the adenylate cyclase system in these cells and may be of general significance to the action of other inhibitory hormones.
D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D002414:Cations, Monovalent; D002460:Cell Line; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D005910:Glioma / Q000201:enzymology; D006160:Guanosine Triphosphate / Q000494:pharmacology*; D006822:Hybrid Cells / Q000201:enzymology; D007700:Kinetics; D008274:Magnesium / Q000494:pharmacology; D015636:Magnesium Chloride; D051379:Mice; D009294:Narcotics / Q000494:pharmacology*; D009447:Neuroblastoma / Q000201:enzymology; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D051381:Rats; D012964:Sodium / Q000494:pharmacology*
D000067956:Adenylyl Cyclase Inhibitors; D002414:Cations, Monovalent; D009294:Narcotics; D015636:Magnesium Chloride; D006160:Guanosine Triphosphate; D012964:Sodium; D010744:Phosphoric Monoester Hydrolases; D020558:GTP Phosphohydrolases; D008274:Magnesium