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Calcium antagonizes the magnesium‐induced high affinity state of the hepatic vasopressin receptor for the agonist interaction
Author(s) -
Wang Hao,
Gopalakrishnan Venkat,
McNeill J. Robert,
Sulakhe Prakash V.,
Triggle Chris R.
Publication year - 1990
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1990.tb12042.x
Subject(s) - vasopressin , agonist , medicine , endocrinology , chemistry , calcium , receptor , antagonist , vasopressin receptor , arginine , biophysics , biology , biochemistry , amino acid
1 The present study describes the role of Ca 2+ in the regulation of the hepatic vasopressin V 1 receptor. With low concentrations of Ca 2+ , there was a small increase in [ 3 H]‐arginine vasopressin ([ 3 H]‐AVP) binding, but above 10 m m , Ca 2+ decreased the binding of this agonist. In contrast, low concentrations of Mg 2+ were associated with a dramatic concentration‐dependent increase in [ 3 H]‐AVP binding, reaching a maximal effect of 650% above control at concentrations ranging between 1–5 m m . At higher concentrations of Mg 2+ , the stimulatory effect of this cation was less pronounced, falling to 210% of control at 100 m m Mg 2+ . Strikingly, Ca 2+ ‐inhibited the stimulatory effect of Mg 2+ in a concentration‐dependent fashion. 2 Saturation binding data revealed that Ca 2+ (2 to 10 m m ) per se promotes the high affinity conformation of the V 1 receptor for the agonist binding with the K D decreased from a control value of 2.3 n m to 0.5 n m in the presence of 10 m m Ca 2+ . This effect was attenuated with an increase in Ca 2+ above 10 m m . With an increase in Ca 2+ to 20 m m , however, the B max for [ 3 H]‐AVP binding was decreased. Ca 2+ also decreased the high affinity/high capacity state ( K D 100 p m ) of the receptor induced by 1 m m Mg 2+ for agonist interaction. 3 [ 3 H]‐V 1 antagonist binding was inhibited by both Ca 2+ and Mg 2+ . The IC 50 values (mean ± s.e.mean) for Ca 2+ and Mg 2+ were 32 ± 8 and 53 ± 9 m m respectively. Maximal inhibition achieved at 100 m m was 29% for Ca 2+ and 42% for Mg 2+ . Both cations decreased the affinity and increased the capacity of the V 1 receptor for the antagonist. 4 The results suggest that the divalent metal ion binding site(s) modulated by Mg 2+ is also accessible to Ca 2+ . Although Ca 2+ opposes the powerful stimulatory effects of Mg 2+ on agonist binding, the effects of Ca 2+ and Mg 2+ on the B max of [ 3 H]‐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 V 1 receptor.