Role of Ca2+ and protein kinase C in the receptor-mediated activation of Na+/H+ exchange in isolated liver cells.

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 α 1 -adrenergic agonists, the Ca 2+ -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 Ca 2+ 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 α 1 -adrenergic agonists or vasoactive peptides relies on the mobilization of intracellular Ca 2+ . In contrast, only the α 1 -adrenergic-agonist-induced alkalinization was dependent on extracellular Ca 2+ . Even though α 1 -adrenergic as well as vasoactive peptide agonists stimulated protein kinase C (PKC) activity in isolated liver cells, only the α 1 -adrenoreceptor-mediated intracellular alkalinization was dependent on PKC. According to these observations, Ca 2+ -mobilizing agonists appear to activate the Na + /H + exchanger by at least two different mechanisms: (1) the α 1 -adrenoreceptor-mediated activation that is dependent on extracellular Ca 2+ and PKC; and (2) vasoactive-peptide-induced alkalinization that is independent of extracellular Ca 2+ and PKC. The α 1 -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.