| First Author | Brown DA | Year | 2003 |
| Journal | Am J Physiol Gastrointest Liver Physiol | Volume | 285 |
| Issue | 5 | Pages | G804-12 |
| PubMed ID | 12842825 | Mgi Jnum | J:108051 |
| Mgi Id | MGI:3622943 | Doi | 10.1152/ajpgi.00150.2003 |
| Citation | Brown DA, et al. (2003) Critical role for NHE1 in intracellular pH regulation in pancreatic acinar cells. Am J Physiol Gastrointest Liver Physiol 285(5):G804-12 |
| abstractText | 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+/H+ exchanger(s) [NHE(s)] is proposed to be integral in the process of fluid secretion both in terms of the transcellular flux of Na+ and intracellular pH (pHi) regulation. Multiple NHE isoforms have been identified in pancreatic tissue, but little is known about their individual functions in acinar cells. The Na+/H+ exchange inhibitor 5-(N-ethyl-N-isopropyl) amiloride completely blocked pHi recovery after an NH4Cl-induced acid challenge, confirming a general role for NHE in pHi regulation. The targeted disruption of the Nhe1 gene also completely abolished pHi recovery from an acid load in pancreatic acini in both HCO3--containing and HCO3--free solutions. In contrast, the disruption of either Nhe2 or Nhe3 had no effect on pHi recovery. In addition, NHE1 activity was upregulated in response to muscarinic stimulation in wild-type mice but not in NHE1-deficient mice. Fluctuations in pHi could potentially have major effects on Ca2+ signaling following secretagogue stimulation; however, the targeted disruption of Nhe1 was found to have no significant effect on intracellular Ca2+ homeostasis. These data demonstrate that NHE1 is the major regulator of pHi in both resting and muscarinic agonist-stimulated pancreatic acinar cells. |
