Modulation of the affinity of the vasopressin receptor by magnesium ions.
The binding of [3H]vasopressin (AVP) and the 125I-labelled vasopressin antagonist (VP-AT) d(CH2)5[Tyr2(Me),Tyr9(NH2)]AVP to rat liver membranes was examined with or without the addition of milimolar concentrations of divalent cations. The binding of vasopressin was enhanced by Mg2+ and Co2+ and markedly decreased by EGTA. The addition of EGTA and Mg2+ together restored the binding to a value similar to that of Mg2+ alone. On the contrary, the addition of Mg2+, Co2+, EGTA, and the combination of EGTA and Mg2+ decreased the binding of VP-AT to rat liver membranes. Kinetic analyses showed that Mg2+ increased the Kd twofold for VP-AT; that is from 0.13 nM to 0.28 nM. Moreover, it showed that the receptor with or without the addition of Mg2+ consists of a single population of binding sites, indicating that the receptor is switched from a high affinity to a low affinity state for VP-AT in the presence of 10 mM Mg2+. GTP gamma S was unable to block the effect of Mg2+ on the binding of VP-AT. These results suggest that this divalent cation interacts with receptor itself producing a conformational changes which thus modulates the affinity of the receptor.
González
C B
CB
Instituto de Fisiología, Universidad Austral de Chile, Valdivia.
Reyes
C E
CE
Caorsi
C E
CE
Troncoso
S
S
D000818:Animals; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000378:metabolism; D002413:Cations, Divalent; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008274:Magnesium / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011945:Receptors, Angiotensin / Q000187:drug effects* / Q000378:metabolism; D017483:Receptors, Vasopressin; D014667:Vasopressins / Q000037:antagonists & inhibitors
D002413:Cations, Divalent; D011945:Receptors, Angiotensin; D017483:Receptors, Vasopressin; D014667:Vasopressins; D001127:Arginine Vasopressin; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D008274:Magnesium