Modulation of binding at opioid receptors by mono- and divalent cations and by cholinergic compounds.
In membrane suspensions from guinea-pig brain, NaCl, LiCl, NH4Cl and KCl, inhibit the equilibrium binding (25 degrees C) of the selective mu-agonist [3H]-[D-Ala2,MePhe4,Gly-ol5]enkephalin, the selective delta-agonist [3H]-[D-Pen2,D-Pen5]enkephalin and the selective kappa-agonist [3H]-dynorphin A (1-9). Choline chloride inhibits the binding of the mu- and kappa-agonists but not of the delta-agonist; the choline derivative, methacholine, inhibits also the binding of the delta-agonist. Binding of the delta-agonist is potentiated by CaCl2, MgCl2 and MnCl2; these salts inhibit binding of the kappa-agonist. As far as binding of the mu-agonist is concerned, MgCl2 and MnCl2 may potentiate or inhibit whereas CaCl2 is only inhibitory. The binding of the mu-antagonist [3H]-naloxone is potentiated by NaCl; while the threshold of inhibition by LiCl is increased there is no potentiation. In membrane suspensions of the rabbit cerebellum about 80% of the opioid binding sites are of the mu-type; the binding of the mu-agonist [3H]-[D-Ala2,MePhe4,Gly-ol5]enkephalin is inhibited by NaCl, LiCl, KCl and choline chloride whereas that of the mu-antagonists [3H]-naloxone and [3H]-(-)-bremazocine is potentiated at low concentrations but inhibited at higher concentrations of NaCl. In membranes of the guinea-pig cerebellum about 80% of the opioid binding sites are of the kappa-type; they are particularly effective for assays of kappa-receptors when the selective kappa-agonist [3H]-dynorphin A (1-9) is used as ligand.
Kosterlitz
H W
HW
Unit for Research on Addictive Drugs, University of Aberdeen, Marischal College, U.K.
Paterson
S J
SJ
Robson
L E
LE
D000818:Animals; D002412:Cations / Q000494:pharmacology*; D006168:Guinea Pigs; D009294:Narcotics / Q000378:metabolism; D011485:Protein Binding; D011817:Rabbits; D051381:Rats; D011957:Receptors, Opioid / Q000187:drug effects* / Q000378:metabolism; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu
D002412:Cations; D009294:Narcotics; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu