Abstract
Morphine (1–100 μm) was found to inhibit several concomitant events in brain slices and synaptosomes which are augmented by depolarizing agents. Thus, 45Ca 2+ uptake, amino acid neurotransmitter release, increases in 3',5' cyclic AMP levels and 32P i incorporation to proteins and lipids induced by veratrine (25 μM) and by potassium (56 mM), were each inhibited in a dose related manner. These inhibitory actions of morphine were all prevented by naloxone (1 μM). 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.
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