{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T10:55:03Z","timestamp":1790506503376,"version":"4.1.0"},"reference-count":57,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"published-print":{"date-parts":[[2003,11]]},"abstract":"<jats:p>The primary function of pancreatic acinar cells is to secrete digestive enzymes together with a NaCl-rich primary fluid which is later greatly supplemented and modified by the pancreatic duct. A Na<jats:sup>+<\/jats:sup>\/H<jats:sup>+<\/jats:sup>exchanger(s) [NHE(s)] is proposed to be integral in the process of fluid secretion both in terms of the transcellular flux of Na<jats:sup>+<\/jats:sup>and intracellular pH (pH<jats:sub>i<\/jats:sub>) regulation. Multiple NHE isoforms have been identified in pancreatic tissue, but little is known about their individual functions in acinar cells. The Na<jats:sup>+<\/jats:sup>\/H<jats:sup>+<\/jats:sup>exchange inhibitor 5-( N-ethyl- N-isopropyl) amiloride completely blocked pH<jats:sub>i<\/jats:sub>recovery after an NH<jats:sub>4<\/jats:sub>Cl-induced acid challenge, confirming a general role for NHE in pH<jats:sub>i<\/jats:sub>regulation. The targeted disruption of the Nhe1 gene also completely abolished pH<jats:sub>i<\/jats:sub>recovery from an acid load in pancreatic acini in both [Formula: see text]-containing and [Formula: see text]-free solutions. In contrast, the disruption of either Nhe2 or Nhe3 had no effect on pH<jats:sub>i<\/jats:sub>recovery. In addition, NHE1 activity was upregulated in response to muscarinic stimulation in wild-type mice but not in NHE1-deficient mice. Fluctuations in pH<jats:sub>i<\/jats:sub>could potentially have major effects on Ca<jats:sup>2+<\/jats:sup>signaling following secretagogue stimulation; however, the targeted disruption of Nhe1 was found to have no significant effect on intracellular Ca<jats:sup>2+<\/jats:sup>homeostasis. These data demonstrate that NHE1 is the major regulator of pH<jats:sub>i<\/jats:sub>in both resting and muscarinic agonist-stimulated pancreatic acinar cells.<\/jats:p>","DOI":"10.1152\/ajpgi.00150.2003","type":"journal-article","created":{"date-parts":[[2015,3,3]],"date-time":"2015-03-03T19:59:21Z","timestamp":1425412761000},"page":"G804-G812","source":"Crossref","is-referenced-by-count":36,"title":["Critical role for NHE1 in intracellular pH regulation in pancreatic acinar cells"],"prefix":"10.1152","volume":"285","author":[{"given":"David A.","family":"Brown","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James E.","family":"Melvin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David I.","family":"Yule","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"REF1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1998.8611"},{"key":"REF2","doi-asserted-by":"publisher","DOI":"10.1097\/00006676-199207000-00001"},{"key":"REF3","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.108.1.35"},{"key":"REF4","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1996.sp021149"},{"key":"REF5","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.7.4383"},{"key":"REF6","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.1990.258.6.G958"},{"key":"REF7","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1993.tb18338.x"},{"key":"REF8","doi-asserted-by":"publisher","DOI":"10.1177\/10454411930040031701"},{"key":"REF9","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1999.276.4.C788"},{"key":"REF10","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1995.269.1.C198"},{"key":"REF11","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(89)92204-3"},{"key":"REF12","unstructured":"Choi JY, Lee MG, Ko S, and Muallem S.Cl--dependent \\batchmode \\documentclass[fleqn,10pt,legalpaper]{article} \\usepackage{amssymb} \\usepackage{amsfonts} \\usepackage{amsmath} \\pagestyle{empty} \\begin{document} \\(\\mathrm{HCO}_{3}^{-}\\) \\end{document} transport by cystic fibrosis transmembrane conductance regulator.J Pancreas2,Suppl: 243-246, 2001."},{"key":"REF13","doi-asserted-by":"publisher","DOI":"10.1038\/35065099"},{"key":"REF14","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.41.29025"},{"key":"REF15","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2001.013453"},{"key":"REF16","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1998.275.3.C810"},{"key":"REF17","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00352.2002"},{"key":"REF18","doi-asserted-by":"crossref","unstructured":"Grynkiewicz G, Poenie M, and Tsien RY.A new generation of Ca2+indicators with greatly improved fluorescence properties.J Biol Chem260: 3440-3450, 1985.","DOI":"10.1016\/S0021-9258(19)83641-4"},{"key":"REF19","doi-asserted-by":"publisher","DOI":"10.1007\/s004240050276"},{"key":"REF20","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.1985.249.1.G125"},{"key":"REF21","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ph.49.030187.000511"},{"key":"REF22","doi-asserted-by":"publisher","DOI":"10.3109\/02713689309001832"},{"key":"REF23","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1989.256.2.C288"},{"key":"REF24","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1990.sp018111"},{"key":"REF25","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1998.341bb.x"},{"key":"REF26","doi-asserted-by":"crossref","unstructured":"Manganel Mand Turner RJ.Agonist-induced activation of Na+\/H+exchange in rat parotid acinar cells is dependent on calcium but not on protein kinase C.J Biol Chem265: 4284-4289, 1990.","DOI":"10.1016\/S0021-9258(19)39560-2"},{"key":"REF27","doi-asserted-by":"crossref","unstructured":"Manganel Mand Turner RJ.Rapid secretagogue-induced activation of Na+H+exchange in rat parotid acinar cells. 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