Divalent cations: do they stabilize the agonist (12S) form of the mu opioid receptor?
In rabbit cerebellum membranes, millimolar concentrations of Mn++ ions while slightly reducing the Kd of 3H-etorphine counteract, to a large extent, sodium inhibition of equilibrium binding of the tritiated agonist to the mu opioid receptor. In digitonin extracts of membranes which have been incubated either with 3H-etorphine or with 3H-diprenorphine in the presence of Mn++ ions, recovery of radioligand bound to the agonist form of the receptor (sedimenting at position 12S) is substantially increased while, at the same time, recovery of radioligand bound to the antagonist form of the receptor (10S) is markedly reduced. Taken together these results suggest that Mn++ ions stabilize the agonist (12S) form of the mu opioid receptor. Mn++ ions may do so by promoting association of the receptor and of a guanine nucleotide regulatory protein.
D000818:Animals; D002413:Cations, Divalent; D002531:Cerebellum / Q000378:metabolism; D005048:Etorphine / Q000378:metabolism; D066298:In Vitro Techniques; D008345:Manganese / Q000494:pharmacology; D011817:Rabbits; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism*; D017450:Receptors, Opioid, mu
D002413:Cations, Divalent; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D005048:Etorphine; D008345:Manganese