Desensitization of opioid-stimulated GTPase in neuroblastoma x glioma hybrid cells.
NG108-15 cells were pretreated with the opioid peptide [D-Ala2, D-Leu5]enkephalin and the opioid-dependent low Km GTPase was assayed in membranes. Pretreatment resulted in a small decrease in basal GTPase activity and led to a concentration-dependent reduction in opioid-mediated stimulation of the enzyme. These effects were observed whether the agonist was present or absent throughout all the experimental procedures, but, in the second condition, the desensitization was smaller. The addition of naloxone had no effect on basal GTPase activity, in either control or pretreated cell membranes. Both Na+ and Mg++ were required for the opioid-induced stimulation of the GTPase. Mg++ enhanced basal enzymatic activity in controls, whereas in membranes from pretreated cells, it produced an inhibition. Thus, desensitization of the opioid-dependent low Km GTPase occurs upon chronic opioid treatment and a Mg++ regulatory site might be altered in the course of this process.
Vachon
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L
Costa
T
T
Herz
A
A
D000818:Animals; D004351:Drug Resistance; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D016308:Enkephalin, Leucine-2-Alanine; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D006822:Hybrid Cells / Q000201:enzymology; D007700:Kinetics; D008274:Magnesium / Q000494:pharmacology; D008566:Membranes / Q000201:enzymology; D009447:Neuroblastoma / Q000201:enzymology*; D009457:Neuroglia / Q000201:enzymology*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D051381:Rats; D012964:Sodium / Q000494:pharmacology
D004743:Enkephalin, Leucine; D016308:Enkephalin, Leucine-2-Alanine; D012964:Sodium; D010744:Phosphoric Monoester Hydrolases; D020558:GTP Phosphohydrolases; D008274:Magnesium