Premium
Mechanism of activation of the NA + /H + exchanger by arginine vasopressin in hepatocytes
Author(s) -
Anwer M. Sawkat
Publication year - 1994
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840200531
Subject(s) - calphostin c , thapsigargin , vasopressin , intracellular ph , intracellular , staurosporine , protein kinase c , sodium–hydrogen antiporter , arginine , chemistry , calcium in biology , phorbol , calphostin , biochemistry , biology , endocrinology , phosphorylation , sodium , organic chemistry , amino acid
Arginine vasopressin has been shown to activate the Na/H + exchanger in hepatocytes by calcium/calmodulin‐dependent processes. Whether this activation also involves protein kinase C and is associated with changes in the intracellular pH setpoint was investigated in this study. Changes in pH i and intracellular Ca ++ concentration were measured with the fluorescent probes BCECF and quin‐2, respectively. Intracellular pH recovery rate was calculated from timedependent changes in intracellular pH in hepatocytes acid‐loaded with sodium propionate. Arginine vasopressin, phorbol myristate acetate and thapsigargin stimulated intracellular pH recovery but did not increased basal intracellular pH. Arginine vasopressin and thapsigargin, but not phorbol myristol acetate, increased intracellular Ca ++ concentration. The protein kinase C inhibitors staurosporine and calphostin C inhibited arginine vasopressin‐ and phorbol myristol acetate—induced, but not thapsigargin‐induced, intracellular pH recovery. Neither staurosporine nor calphostin C affected arginine vasopressin‐ and thapsigargin‐induced increases in intracellular Ca ++ concentration, and no inhibitor affected basal intracellular pH recovery. Arginine vasopressin, phorbol myristol acetate and thapsigargin increased intracellular pH dependency of intracellular pH recovery without affecting intracellular pH setpoint. These results indicate that the activation of the Na + /H + exchanger by arginine vasopressin is mediated both by Ca ++ /calmodulin and protein kinase C and may be due to enhanced interaction of H + with the internal modifier site of the exchanger. (Hepatology 1994;20:1309–1317).