Advertisement

Research Article Free access | 10.1172/JCI118109

Effect of glucagon on intracellular pH regulation in isolated rat hepatocyte couplets.

D Alvaro, P Della Guardia, A Bini, A Gigliozzi, S Furfaro, T La Rosa, C Piat, and L Capocaccia

II Department of Gastroenterology, University of Rome La Sapienza, Italy.

Find articles by Alvaro, D. in: PubMed | Google Scholar

II Department of Gastroenterology, University of Rome La Sapienza, Italy.

Find articles by Della Guardia, P. in: PubMed | Google Scholar

II Department of Gastroenterology, University of Rome La Sapienza, Italy.

Find articles by Bini, A. in: PubMed | Google Scholar

II Department of Gastroenterology, University of Rome La Sapienza, Italy.

Find articles by Gigliozzi, A. in: PubMed | Google Scholar

II Department of Gastroenterology, University of Rome La Sapienza, Italy.

Find articles by Furfaro, S. in: PubMed | Google Scholar

II Department of Gastroenterology, University of Rome La Sapienza, Italy.

Find articles by La Rosa, T. in: PubMed | Google Scholar

II Department of Gastroenterology, University of Rome La Sapienza, Italy.

Find articles by Piat, C. in: PubMed | Google Scholar

II Department of Gastroenterology, University of Rome La Sapienza, Italy.

Find articles by Capocaccia, L. in: PubMed | Google Scholar

Published August 1, 1995 - More info

Published in Volume 96, Issue 2 on August 1, 1995
J Clin Invest. 1995;96(2):665–675. https://doi.org/10.1172/JCI118109.
© 1995 The American Society for Clinical Investigation
Published August 1, 1995 - Version history
View PDF
Abstract

To elucidate mechanisms of glucagon-induced bicarbonate-rich choleresis, we investigated the effect of glucagon on ion transport processes involved in the regulation of intracellular pH (pHi) in isolated rat hepatocyte couplets. It was found that glucagon (200 nM), without influencing resting pHi, significantly stimulates the Cl-/HCO3- exchange activity. The effect of glucagon was associated with a sevenfold increase in cAMP levels in rat hepatocytes. The activity of the Cl-/HCO3- exchanger was also stimulated by DBcAMP + forskolin. The effect of glucagon on the Cl-/HCO3- exchange was individually blocked by two specific and selective inhibitors of protein kinase A, Rp-cAMPs (10 microM) and H-89 (30 microM), the latter having no influence on the glucagon-induced cAMP accumulation in isolated rat hepatocytes. The Cl- channel blocker, NPPB (10 microM), showed no effect on either the basal or the glucagon-stimulated Cl-/HCO3 exchange. In contrast, the protein kinase C agonist, PMA (10 microM), completely blocked the glucagon stimulation of the Cl-/HCO3- exchange; however, this effect was achieved through a significant inhibition of the glucagon-stimulated cAMP accumulation in rat hepatocytes. Colchicine pretreatment inhibited the basal as well as the glucagon-stimulated Cl-/HCO3- exchange activity. The Na+/H+ exchanger was unaffected by glucagon either at basal pHi or at acid pHi values. In contrast, glucagon, at basal pHi, stimulated the Na(+)-HCO3- symport. The main findings of this study indicate that glucagon, through the cAMP-dependent protein kinase A pathway, stimulates the activity of the Cl-/HCO3- exchanger in isolated rat hepatocyte couplets, a mechanism which could account for the in vivo induced bicarbonate-rich choleresis.

Images.

Browse pages

Click on an image below to see the page. View PDF of the complete article

Version history
  • Version 1 (August 1, 1995): No description
Advertisement
Advertisement