The effect of morphine on the endogenous phosphorylation of synaptic plasma membrane proteins of rat striatum.
The synaptic plasma membrane (SPM) fraction was prepared from rat striata and assayed for endogenous phosphorylation in vitro. After the separation of membrane proteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the incorporation of phosphate into specific membrane proteins was analyzed by gel slicing and autoradiographic techniques. Phosphate was incorporated into several SPM protein bands, two of which were regulated by cyclic adenosine 3':5' monophosphate. As a consequence of the chronic (in vivo) administration of morphine, the phosphorylation of two protein bands, designated protein II (MW 48,000-52,000) and protein III (MW 11,000-18,000), was reduced by approximately 20 and 50%, respectively; the phosphorylation of the former proteins was regulated by cyclic adenosine monophosphate whereas the phosphorylation of the latter proteins was not. The incorporation of phosphate into these same two protein bands was similar to control values when the membranes were obtained from rats undergoing naloxone-precipitated withdrawal. Morphine, in vitro, did not alter the phosphorylation of any SPM proteins in the assay, although at a high concentration morphine did antagonize the calcium-stimulated phosphorylation of one or more proteins in band II. The development of tolerance to and dependence on opiates may include changes in the phosphorylation of specific SPM proteins.
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D066298:In Vitro Techniques; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008970:Molecular Weight; D009020:Morphine / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D013570:Synaptic Membranes / Q000187:drug effects / Q000378:metabolism*
D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D009020:Morphine