Characterization of muscarinic cholinergic receptors in the brains of copper-deficient rats.
In order to assess a possible role for copper as a regulator of muscarinic receptors in vitro, the receptor was characterized in rats made copper deficient by a dietary regimen. In forebrain regions there was a decrease in both the affinity of the receptors for [3H]-1-quinuclidinyl benzilate and the density of receptors in the copper-deficient animals compared with control animals. Copper treatment in vitro of homogenates from deficient animals did not reverse the in vivo effects on antagonist binding but, rather, decreased receptor occupancy and ligand affinity in a manner similar to copper treatment of control homogenates. Minimally deficient rats displayed very similar changes in receptor properties compared with the more severely deficient animals. Minimal copper deficiency produced robust effects on the binding of agonists, increasing ID50 and derived dissociation constants. The addition of copper to the assay medium caused an apparent reversal of the in vivo effect of copper deficiency on agonist binding, decreasing ID50 and derived dissociation constants to values near those observed with homogenates from normal animals in the presence of copper. Since copper deficiency has dramatic effects on both receptor number and the binding of agonists to muscarinic receptors in the central nervous system, it is suggested that copper, because of its ability to form complexes with some proteins, may have an endogenous role in the regulation of the receptor.
D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000648:ultrastructure; D002217:Carbachol / Q000494:pharmacology; D003300:Copper / Q000172:deficiency* / Q000494:pharmacology; D005260:Female; D008297:Male; D008670:Metals / Q000378:metabolism; D009696:Nucleic Acids / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*
D008670:Metals; D009696:Nucleic Acids; D011976:Receptors, Muscarinic; D003300:Copper; D002217:Carbachol