Effect of HCO(3)(-) on TPA- and IBMX-induced anion conductances in Necturus gallbladder epithelial cells.
Effects of HCO(3)(-) on protein kinase C (PKC)- and protein kinase A (PKA)-induced anion conductances were investigated in Necturus gallbladder epithelial cells. In HCO(3)(-)-free media, activation of PKC via 12-O-tetradecanoylphorbol 13-acetate (TPA) depolarized apical membrane potential (V(a)) and decreased fractional apical voltage ratio (F(R)). These effects were blocked by mucosal 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB), a Cl(-) channel blocker. In HCO(3)(-) media, TPA induced significantly greater changes in V(a) and F(R). These effects were blocked only when NPPB was present in both mucosal and basolateral compartments. The data suggest that TPA activates NPPB-sensitive apical Cl(-) conductance (g(Cl)(a)) in the absence of HCO(3)(-); in its presence, TPA stimulated both NPPB-sensitive g(Cl)(a) and basolateral Cl(-) conductance (g(Cl)(b)). Activation of PKA via 3-isobutyl-1-methylxanthine (IBMX) also decreased V(a) and F(R); however, these changes were not affected by external HCO(3)(-). We conclude that HCO(3)(-) modulates the effects of PKC on g(Cl)(b). In HCO(3)(-) medium, TPA and IBMX also induced an initial transient hyperpolarization and increase in intracellular pH. Because these changes were independent of mucosal Na(+) and Cl(-), it is suggested that TPA and IBMX induce a transient increase in apical HCO(3)(-) conductance.
Lyall
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Department of Physiology and Biophysics, Indiana University School of Medicine, Indianapolis, Indiana 46202-5102, USA.
Armstrong
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WM
Lyall
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D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology*; D000818:Animals; D000838:Anions / Q000378:metabolism*; D001639:Bicarbonates / Q000494:pharmacology*; D004553:Electric Conductivity; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology; D005704:Gallbladder / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D009338:Necturus maculosus; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D000838:Anions; D001639:Bicarbonates; D013755:Tetradecanoylphorbol Acetate; D015056:1-Methyl-3-isobutylxanthine