title: Different rate-limiting activities of intracellular pH regulators for HCO3-secretion stimulated by forskolin and carbachol in rat parotid intralobular ducts.
abstract: 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 pHiregulation for HCO3-secretion by cAMP and Ca2+signals. Resting pHiwas dispersed between 7.4 and 7.9. Forskolin consistently decreased pHishowing the dominance of pHi-lowering activities, but carbachol gathered pHiaround 7.6. CA inhibition suppressed the forskolin-induced decrease in pHi, while it allowed carbachol to consistently increase pHiby 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 pHifor HCO3-secretion.
authors.affiliation: Department of Physiology and Oral Physiology, Institute of Biomedical and Health Sciences, Hiroshima University, 2-3 Kasumi 1-Chome, Minami-ku, Hiroshima, 734-8553, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Ueno
authors.affiliation: Department of Physiology and Oral Physiology, Institute of Biomedical and Health Sciences, Hiroshima University, 2-3 Kasumi 1-Chome, Minami-ku, Hiroshima, 734-8553, Japan. chikara@hiroshima-u.ac.jp.
authors.forename: Chikara
authors.identifier: http://orcid.org/0000-0002-2134-7375
authors.initials: C
authors.lastname: Hirono
authors.affiliation: Department of Physiology and Oral Physiology, Institute of Biomedical and Health Sciences, Hiroshima University, 2-3 Kasumi 1-Chome, Minami-ku, Hiroshima, 734-8553, Japan.
authors.forename: Michinori
authors.initials: M
authors.lastname: Kitagawa
authors.affiliation: Department of Physiology and Oral Physiology, Institute of Biomedical and Health Sciences, Hiroshima University, 2-3 Kasumi 1-Chome, Minami-ku, Hiroshima, 734-8553, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Shiba
authors.affiliation: Department of Physiology and Oral Physiology, Institute of Biomedical and Health Sciences, Hiroshima University, 2-3 Kasumi 1-Chome, Minami-ku, Hiroshima, 734-8553, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Sugita
mesh_terms: D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology*; D005576:Colforsin / Q000494:pharmacology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000037:antagonists & inhibitors; D004533:Egtazic Acid / Q000031:analogs & derivatives; D004847:Epithelial Cells / Q000378:metabolism; D005452:Fluoresceins; D006863:Hydrogen-Ion Concentration; D008704:Methazolamide / Q000494:pharmacology; D010306:Parotid Gland / Q000166:cytology* / Q000378:metabolism*; D051381:Rats
chemical_list: D001639:Bicarbonates; C579654:CFTR protein, rat; D005452:Fluoresceins; C057433:2',7'-bis-(2-carboxyethyl)-5(6)-carboxyfluorescein acetoxymethyl ester; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D005576:Colforsin; D004533:Egtazic Acid; D002217:Carbachol; D008704:Methazolamide
keywords: Bicarbonate secretion; Carbonic anhydorase; Cl− channels; Intracellular pH; Na+–H+ exchanger; Rat parotid intralobular ducts