Sodium regulation of opioid agonist binding is potentiated by pertussis toxin.
Pretreatment of intact NG108-15 cells with pertussis toxin suppresses opioid inhibition of cyclic AMP accumulation mediated by the inhibitory guanine nucleotide-binding regulatory protein, Ni, which apparently also mediates the inhibitory nucleotide effects on opioid against binding. The toxin treatment had no effect on opioid agonist binding measured in NG108-15 cell membranes without sodium present. However, the toxin potentiated the inhibitory effect of sodium on agonist binding, leading to an agonist-specific reduction of opioid receptor affinity in the presence of sodium in the binding reaction. The potency of the stable GTP analog, GTP gamma S, to reduce agonist binding in the presence of sodium was little changed in membranes prepared from pertussis toxin-treated cells compared to control membranes, whereas the potency of the stable GDP analog, GDP beta S, was magnified. The data indicate that ADP-ribosylation of Ni by pertussis toxin potentiates sodium regulation of opioid agonist binding and that the communication between Ni and opioid receptors is not lost by the covalent modification of Ni.
D000818:Animals; D001427:Bacterial Toxins / Q000494:pharmacology*; D002460:Cell Line; D004174:Diprenorphine / Q000378:metabolism / Q000494:pharmacology*; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D016308:Enkephalin, Leucine-2-Alanine; D005910:Glioma; D006150:Guanine Nucleotides / Q000494:pharmacology; D006822:Hybrid Cells / Q000378:metabolism; D051379:Mice; D009019:Morphinans / Q000494:pharmacology*; D009447:Neuroblastoma; D037342:Pertussis Toxin; D051381:Rats; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism*; D012964:Sodium / Q000494:pharmacology*; D010566:Virulence Factors, Bordetella
D001427:Bacterial Toxins; D006150:Guanine Nucleotides; D009019:Morphinans; D011957:Receptors, Opioid; D010566:Virulence Factors, Bordetella; D004174:Diprenorphine; D004743:Enkephalin, Leucine; D016308:Enkephalin, Leucine-2-Alanine; D012964:Sodium; D037342:Pertussis Toxin