Different rate-limiting activities of intracellular pH regulators for HCO 3 − secretion stimulated by forskolin and carbachol in rat parotid intralobular ducts

Abstract

Intracellular pH (pH_i) regulation fundamentally participates in maintaining HCO₃⁻ release from HCO₃⁻-secreting epithelia. We used parotid intralobular ducts loaded with BCECF to investigate the contributions of a carbonic anhydrase (CA), anion channels and a Na⁺–H⁺ exchanger (NHE) to pH_i regulation for HCO₃⁻ secretion by cAMP and Ca²⁺ signals. Resting pH_i was dispersed between 7.4 and 7.9. Forskolin consistently decreased pH_i showing the dominance of pH_i-lowering activities, but carbachol gathered pH_i around 7.6. CA inhibition suppressed the forskolin-induced decrease in pH_i, while it allowed carbachol to consistently increase pH_i by revealing that carbachol prominently activated NHE via Ca²⁺-calmodulin. Under NHE inhibition, forskolin and carbachol induced the remarkable decreases in pH_i, which were slowed predominantly by CA inhibition and by CA or anion channel inhibition, respectively. Our results suggest that forskolin and carbachol primarily activate the pH_i-lowering CA and pH_i-raising NHE, respectively, to regulate pH_i for HCO₃⁻ secretion.

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