title: Opiates, cyclic nucleotides, and xanthines.
abstract: In rat brain homogenate, opiates exert a dose-related inhibition of PGE-stimulated cyclic (AMP) formation. This effect is stereospecific and is correlated with agonist potency. Naloxone antagonizes heroid in a dose-related way, without, at effective concentrations, itself inhibiting PGE-stimulated cyclic AMP formation. In morphine-dependent rats, intracerebroventricular injection of cyclic AMP intensifies and of dibutyryl cyclic GMP diminishes precipitated abstinence effects. In naive rats, the xanthines, theophylline and 3-isobutyl-1-methylxanthine, produce a quasimorphine-abstinence syndrome that is readily suppressed by heroin and intensified by nalosone. In rat brain homogenate, these xanthines inhibit cyclic AMP phosphodiesterase. These findings are concistent with these views: (a) The opiates specifically inhibit an adenylate cyclase of morphine-sensitive neurons that is sensitive to stimulation by PGEs. (b) Opiate agonist action is associated with the lowering of a neuronal cyclic AMP. (c) Both the morphine-abstinence syndrome in dependent rats and the quasi-abstinence syndrome in naive rats are associated with a rise in this neuronal cyclic AMP. (d) There are two types of endogenous humoral mediator acting on morphine-sensitive neurons, one of which is morphine-like and the other antimorphine-like in action.
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D002110:Caffeine / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D004298:Dopamine / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000201:enzymology; D009020:Morphine / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D011458:Prostaglandins E / Q000494:pharmacology; D013806:Theophylline / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology*
chemical_list: D009294:Narcotics; D011458:Prostaglandins E; D014970:Xanthines; D002110:Caffeine; D009020:Morphine; D013806:Theophylline; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D000262:Adenylyl Cyclases; D004298:Dopamine