title: Role of Ca2+ and protein kinase C in the receptor-mediated activation of Na+/H+ exchange in isolated liver cells.
abstract: This work aimed to study the relationship between agonist-induced changes in cytosolic free calcium levels, protein kinase C (PKC) activity and intracellular pH in isolated liver cells. We observed that, like alpha1-adrenergic agonists, the Ca2+-mobilizing vasoactive peptides vasopressin and angiotensin II produced an extracellular-Na+-dependent, 5-(N-ethyl-N-isopropyl)amiloride-sensitive, intracellular alkalinization, indicative of Na+/H+ antiporter activation. Blocking the agonist-induced increase in the intracellular Ca2+ concentration using the calcium chelator bis-(o-aminophenoxy)ethane-N,N,N', N'-tetra-acetic acid (BAPTA) prevented all types of receptor-mediated intracellular alkalinization. Thus activation of the Na+/H+ exchanger by either alpha1-adrenergic agonists or vasoactive peptides relies on the mobilization of intracellular Ca2+. In contrast, only the alpha1-adrenergic-agonist-induced alkalinization was dependent on extracellular Ca2+. Even though alpha1-adrenergic as well as vasoactive peptide agonists stimulated protein kinase C (PKC) activity in isolated liver cells, only the alpha1-adrenoreceptor-mediated intracellular alkalinization was dependent on PKC. According to these observations, Ca2+-mobilizing agonists appear to activate the Na+/H+ exchanger by at least two different mechanisms: (1) the alpha1-adrenoreceptor-mediated activation that is dependent on extracellular Ca2+ and PKC; and (2) vasoactive-peptide-induced alkalinization that is independent of extracellular Ca2+ and PKC. The alpha1-adrenoreceptor-mediated, PKC-sensitive, activation of the Na+/H+ exchanger seems to be responsible for the distinct ability of these receptors to elicit the sustained stimulation of hepatic functions.
authors.affiliation: Department of Pathophysiology and Human Molecular Genetics, Centro de Investigaciones Biológicas (CSIC), Velázquez 144, 28006-Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Martín-Requero
authors.forename: F J
authors.initials: FJ
authors.lastname: Daza
authors.forename: O G
authors.initials: OG
authors.lastname: Hermida
authors.forename: N
authors.initials: N
authors.lastname: Butta
authors.forename: R
authors.initials: R
authors.lastname: Parrilla
mesh_terms: D058646:Adrenergic alpha-1 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002147:Calmodulin / Q000494:pharmacology; D004789:Enzyme Activation; D006863:Hydrogen-Ion Concentration; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*; D014667:Vasopressins / Q000494:pharmacology
chemical_list: D058646:Adrenergic alpha-1 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D002147:Calmodulin; D017923:Sodium-Hydrogen Exchangers; D014667:Vasopressins; D000804:Angiotensin II; D011493:Protein Kinase C; D002118:Calcium