The possible role of protein phosphatase 2A in the sodium sensitivity of the receptor binding of opiate antagonists naloxone and naltrindole.
In striatal membrane preparation used for receptor binding experiments high levels of protein phosphatase 1 and 2A activities were detected using [32P]phosphorylase a as substrate. Sodium chloride decreased the activity of protein phosphatase 2A and increased the activity of protein phosphatase 1 in a concentration-dependent manner. Sodium chloride facilitated the saturation binding of naloxone and naltrindole in rat striatal membrane preparation preincubated with ATP (50 microM) and MgCl2 (5 mM). Preincubation with calyculin A (1 nM) further increased the binding of naloxone. Addition of okadaic acid in a concentration of 2 nM, which is specific for the inhibition of protein phosphatase 2A, augmented the number of binding sites of naloxone or naltrindole. The results suggest a protein phosphatase-dependent regulation of the binding of opiate ligands in the striatum.
Murányi
A
A
Department of Medical Chemistry, University Medical School of Debrecen, Hungary.
Gergely
P
P
Nagy
G M
GM
Fekete
M I
MI
D000818:Animals; D003342:Corpus Striatum / Q000737:chemistry / Q000201:enzymology; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D008387:Marine Toxins; D009270:Naloxone / Q000378:metabolism / Q000494:pharmacology*; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000378:metabolism / Q000494:pharmacology*; D010080:Oxazoles / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010761:Phosphorus Radioisotopes; D010762:Phosphorylase a / Q000494:pharmacology; D054645:Protein Phosphatase 1; D054648:Protein Phosphatase 2; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000378:metabolism; D012680:Sensitivity and Specificity; D012965:Sodium Chloride / Q000494:pharmacology*; D013379:Substrate Specificity; D014316:Tritium
D004791:Enzyme Inhibitors; D008387:Marine Toxins; D009292:Narcotic Antagonists; D010080:Oxazoles; D010761:Phosphorus Radioisotopes; D011957:Receptors, Opioid; D014316:Tritium; D009270:Naloxone; D012965:Sodium Chloride; D009271:Naltrexone; C059041:calyculin A; D010762:Phosphorylase a; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D054648:Protein Phosphatase 2; C055382:naltrindole