title: Essential role of magnesium in oxytocin-receptor affinity and ligand specificity.
abstract: We have analysed, with the aid of a novel radioiodinated oxytocin (OT)-receptor antagonist, the role of Mg2+ in uterine OT-receptor function. The antagonist-receptor interaction was characterized by high affinity, reversibility and stereospecificity in Tris/HCl buffer containing 3 mmol of Mg2+/litre as well as buffer free of Mg2+. By contrast, omission of Mg2+ decreased the affinity of the receptor for OT by about 1500-fold; moreover, the stereospecificity of agonist, but not antagonist, binding was lost. Since guanine nucleotides had relatively minor effects in this system (less than or equal to 2-fold decrease in OT affinity), we suggest that the agonist-binding site of OT receptors is directly modulated by Mg2+, unlike other receptors, where the effects of bivalent cations are exerted via guanine-nucleotide-binding (G-) proteins. Thus the ligand recognition mechanism of OT receptors may be novel in this respect.
authors.affiliation: Department of Human Anatomy, University of Oxford, U.K.
authors.forename: F A
authors.initials: FA
authors.lastname: Antoni
authors.forename: S E
authors.initials: SE
authors.lastname: Chadio
mesh_terms: D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D003035:Cobalt / Q000378:metabolism; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism; D008024:Ligands / Q000378:metabolism; D008274:Magnesium / Q000378:metabolism*; D008345:Manganese / Q000378:metabolism; D008566:Membranes / Q000378:metabolism; D010121:Oxytocin / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011945:Receptors, Angiotensin / Q000378:metabolism*; D018045:Receptors, Oxytocin; D014599:Uterus / Q000378:metabolism
chemical_list: D008024:Ligands; D011945:Receptors, Angiotensin; D018045:Receptors, Oxytocin; D003035:Cobalt; D008345:Manganese; D010121:Oxytocin; D019204:GTP-Binding Proteins; D008274:Magnesium; D002118:Calcium