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


MeSH Major

  • Arginine Vasopressin
  • Calcium
  • Liver
  • Magnesium
  • Receptors, Angiotensin
  • Receptors, Vasopressin


  • 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 KD 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 Bmax for [3H]-AVP binding was decreased. Ca2+ also decreased the high affinity/high capacity state (KD 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,,x 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.

publication date

  • January 1990



  • Academic Article



  • eng

PubMed Central ID

  • PMC1917482

PubMed ID

  • 2372661

Additional Document Info

start page

  • 5

end page

  • 10


  • 100


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