Effects of Opiates on High‐Affinity Ca2+,Mg2+‐ATPase in Brain Membrane Subfractions

The effect of a single administration of morphine sulfate (15 mg/kg, s.c. or 30 mg/kg, i.p., 30 min) on Ca2+‐stimulated Mg2+‐dependent ATPase activity was investigated in synaptosomal plasma membranes (SPM) prepared from rat cortex. Morphine produced a significant decrease in Ca2+,Mg2+‐ATPase activity in synaptosomal fractions (SPM 1 + 2) known to contain a high density of opiate receptors and calmodulin‐dependent Ca2+,Mg2+‐ATPase. However, in another subpopulation (SPM 3) that contains fewer opiate receptors and less enzyme activity, no such decrease in the enzyme activity was observed after the opiate administration. The decrease in Ca2+,Mg2+‐ATPase activity seen in SPM 1 + 2 was specifically antagonized by the opiate antagonist naloxone hydrochloride (2 mg/kg, s.c.) when given 15 min before morphine administration. Mg2+‐ATP‐ase was not altered either by morphine or by a naloxone‐morphine combination. These findings give further evidence for the role of intracellular Ca2+ in mediating many of the acute effects of opiates.