title: Intracellular calcium-mediated activation of hepatic Na+/H+ exchange by arginine vasopressin and phenylephrine.
abstract: The effect of Ca++ mobilizing agonists arginine vasopressin and phenylephrine on Na+/H+ exchange was studied in freshly isolated hepatocytes and isolated perfused rat livers. The activity of Na+/H+ exchange was determined from the rate of H+ efflux, 22Na uptake and pHi recovery. Arginine vasopressin and phenylephrine stimulated H+ efflux and 22Na uptake in isolated rat hepatocytes and increased the rate of pHi recovery from acid-loaded hepatocytes. These effects were inhibited by amiloride. Arginine vasopressin- and phenylephrine-induced increases in H+ efflux were also dependent on extracellular Na+. Arginine vasopressin- and phenylephrine-induced increases in intracellular Ca++ concentration, H+ efflux, 22Na uptake and intracellular pH recovery were decreased in hepatocytes preloaded with the Ca(++)-buffering agent [bis-(2-amino-5-methylphenoxy)-ethane-N,N,N',N'-tetraacetic acid] (MAPTA). Na+/H+ exchange-dependent intracellular pH recovery from cytosolic acidification was stimulated by thapsigargin, which increases intracellular calcium concentration by inhibiting endoplasmic reticulum Ca++ ATPase. Arginine vasopressin- and phenylephrine-induced increases in intracellular pH recovery were not dependent on extracellular Ca++ and were inhibited by calmidazolium, a calmodulin inhibitor. Arginine vasopressin and phenylephrine also increased H+ efflux in the absence but not in the presence of amiloride in perfused rat livers without affecting biliary HCO3- excretion. These results indicate that arginine vasopressin and phenylephrine activate Na+/H+ exchange in rat hepatocytes, an effect mediated in part by intracellular Ca++ and calmodulin kinase. Furthermore, sinusoidal Na+/H+ exchange does not appear to be involved in biliary HCO3- excretion.
authors.affiliation: Department of Medicine, Tufts University School of Veterinary Medicine, North Grafton, Massachusetts 01536.
authors.forename: M S
authors.initials: MS
authors.lastname: Anwer
authors.forename: J M
authors.initials: JM
authors.lastname: Atkinson
mesh_terms: D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology*; D002352:Carrier Proteins / Q000378:metabolism*; D006859:Hydrogen / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D010477:Perfusion; D010656:Phenylephrine / Q000494:pharmacology*; D051381:Rats; D012964:Sodium / Q000493:pharmacokinetics; D017923:Sodium-Hydrogen Exchangers
chemical_list: D002352:Carrier Proteins; D017923:Sodium-Hydrogen Exchangers; D001127:Arginine Vasopressin; D010656:Phenylephrine; D006859:Hydrogen; D012964:Sodium; D002118:Calcium