Different rate-limiting activities of intracellular pH regulators for HCO3 − secretion stimulated by forskolin and carbachol in rat parotid intralobular ducts
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Intracellular pH (pHi) 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 pHi regulation for HCO3 − secretion by cAMP and Ca2+ signals. Resting pHi was dispersed between 7.4 and 7.9. Forskolin consistently decreased pHi showing the dominance of pHi-lowering activities, but carbachol gathered pHi around 7.6. CA inhibition suppressed the forskolin-induced decrease in pHi, while it allowed carbachol to consistently increase pHi by revealing that carbachol prominently activated NHE via Ca2+-calmodulin. Under NHE inhibition, forskolin and carbachol induced the remarkable decreases in pHi, 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 pHi-lowering CA and pHi-raising NHE, respectively, to regulate pHi for HCO3 − secretion.
KeywordsIntracellular pH Rat parotid intralobular ducts Bicarbonate secretion Na+–H+ exchanger Carbonic anhydorase Cl− channels
This work was carried out partially at the Analysis Center of Life Science, Natural Science Center for Basic Research and Development, Hiroshima University.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All procedures performed in studies involving animals were in accordance with the ethical standards of the institution at which the studies were conducted.
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