Changes in extra-and intracellular pH in hepatocytes exposed to gabexate mesilate

R. Imberti, A. Ferrigno, A. Tartaglia, V. Rizzo, P. Richelmi, M. Vairetti

Research output: Contribution to journalArticlepeer-review

Abstract

Gabexate mesilate (GM) is a synthetic inhibitor of plasmatic and pancreatic serine proteases licensed for the treatment of pancreatitis. Here we show that in suspensions of isolated hepatocytes, profound changes in extracellular, cytoplasmic, and vesicular pH occur after addition of GM. Isolated hepatocytes obtained by collagenase perfusion of rat liver were pre-incubated with 1,2, and 4 mM GM. Extracellular pH (pH in the incubation medium) was measured by a conventional pH electrode, cytosolic and vesicular pH were measured by fluorescence changes of 2',7'-biscarboxyethyl-5,6-carboxyfiuorescein acetoxymethyl ester (BCECF-AM) and fluorescein dextran, respectively. Incubation of hepatocytes with GM resulted in a dose-dependent decrease of extracellular pH. Cytosolic pH decreased rapidly and markedly in a dose-dependent manner during the first minutes and gradually returned towards baseline. Simultaneously, GM induced a rapid alkalinization of acidic vesicles. The presence of bis-(p-nitrophelyl) phosphate (BNPP), an esterase inhibitor, reduced the extent of extracellular acidification. Incubation of hepatocytes in the presence of dimethylamiloride, an Na7H+ exchanger inhibitor, or in a sodium-free medium, did not modify the rate and extent of extracellular acidification. GM, a commercially available pharmacological agent, could be useful to manipulate extra- And intracellular pH.

Original languageEnglish
Pages (from-to)365-370
Number of pages6
JournalInternational Journal of Immunopathology and Pharmacology
Volume27
Issue number3
Publication statusPublished - Jul 1 2014

Keywords

  • Cytosolic pH
  • Extracellular pH
  • Gabexate mesilate
  • Hepatocytes
  • PH
  • Vesicular pH

ASJC Scopus subject areas

  • Pharmacology
  • Immunology
  • Immunology and Allergy

Fingerprint Dive into the research topics of 'Changes in extra-and intracellular pH in hepatocytes exposed to gabexate mesilate'. Together they form a unique fingerprint.

Cite this