Influence of morphine, β-endorphin and naloxone on the synthesis of phosphoinositides in the rat midbrain

The effect of morphine, β-endorphin and naloxone on the initial incorporation of ³²Pi and [³H]glycerol into TPI, DPI and PI were measured in discrete subcellular fractions of the rat midbrain. Morphine and β-endorphin significantly increased microsomal ³²Pi incorporation into TPI and PI but not DPI. Although neither morphine nor β-endorphin significantly affected the levels of [³H]TPI or [³H]DPI, both agents significantly increased [³H]PI levels. All of the significant effects induced by morphine were blocked by naloxone treatment and were decreased after chronic morphine administration. However, naloxone treatment alone also mimicked all the effects of morphine except the increased incorporation of [³H]glycerol into PI. It was also found that chronic morphine treatment significantly increased the incorporation of ³²Pi into synaptic TPI and DPI. This effect, however, did not show regional specificity being found in both cortical and subcortical synaptic membranes. Overall, the results suggest that the mechanisms of opioid action are closely associated with changes in the turnover of the brain phosphoinositides.