Morphine inhibition of calcium fluxes, neurotransmitter release and protein and lipid phosphorylation in brain slices and synaptosomes.

Morphine (1-100 microM) was found to inhibit several concomitant events in brain slices and synaptosomes which are augmented by depolarizing agents. Thus, 45Ca2+ uptake, amino acid neurotransmitter release, increases in 3',5' cyclic AMP levels and 32Pi incorporation to proteins and lipids induced by veratrine (25 microM) and by potassium (56 mM), were each inhibited in a dose related manner. These inhibitory actions of morphine were all prevented by naloxone (1 microM). Evidence is presented that morphine binding to a receptor on the synaptic membrane affects intracellular mechanisms involved in neurotransmitter release possibly via a second messenger system. An enhancing action of GTP on the inhibitory influences of morphine suggests that its actions are mediated at least in part, via a coupling of the receptor to adenyl cyclase in the outer membrane. This is supported by its inhibitory action on the capacity of depolarizing agents to increase cyclic AMP levels.