Calcium antagonizes the magnesium-induced high affinity state of the hepatic vasopressin receptor for the agonist interaction

H. Wang, V. Gopalakrishnan, J. R. McNeill, P. V. Sulakhe, Christopher Triggle

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Abstract

1. The present study describes the role of Ca2+ in the regulation of the hepatic vasopressin V1 receptor. With low concentrations of Ca2+, there was a small increase in [3H]-arginine vasopressin ([3H]-AVP) binding, but above 10 mM, Ca2+ decreased the binding of this agonist. In contrast, low concentrations of Mg2+ were associated with a dramatic concentration-dependent increase in [3H]-AVP binding, reaching a maximal effect of 650% above control at concentrations ranging between 1-5 mM. At higher concentrations of Mg2+, the stimulatory effect of this cation was less pronounced, falling to 210% of control at 100 mM Mg2+. Strikingly, Ca2+-inhibited the stimulatory effect of Mg2+ in a concentration-dependent fashion. 2. Saturation binding data revealed that Ca2+ (2 to 10 mM) per se promotes the high affinity conformation of the V1 receptor for the agonist binding with the K(D) decreased from a control value of 2.3 nM to 0.5 nM in the presence of 10 mM Ca2+. This effect was attenuated with an increase in Ca2+ above 10 mM. With an increase in Ca2+ to 20 mM, however, the B(max) for [3H]-AVP binding was decreased. Ca2+ also decrased the high affinity/high capacity state (K(D) 100 pM) of the receptor induced by 1 mM Mg2+ for agonist interaction. 3. [3H]-V1 antagonist binding was inhibited by both Ca2+ and Mg2+. The IC50 values (mean ± s.e.mean) for Ca2+ and Mg2+ were 32±8 and 53±9 mM respectively. Maximal inhibition achieved at 100 mM was 29% for Ca2+ and 42% for Mg2+. Both cations decreased the affinity and increased the capacity of the V1 receptor for the antagonist. 4. The results suggest that the divalent metal ion binding site(s) modulated by Mg2+ is also accessible to Ca2+. Although Ca2+ opposes the powerful stimulatory effects of Mg2+ on agonist binding, the effects of Ca2+ and Mg2+ on the B(max) of [3H]-AVP binding were different, suggesting that the divalent cations may bind to two different sites, thereby regulating the affinity and the capacity characteristics of the V1 receptor.

Original languageEnglish
Pages (from-to)5-10
Number of pages6
JournalBritish Journal of Pharmacology
Volume100
Issue number1
Publication statusPublished - 1990
Externally publishedYes

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ASJC Scopus subject areas

  • Pharmacology

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