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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.
D Alvaro, and
P Della Guardia, and
A Bini, and
A Gigliozzi, and
S Furfaro, and
T La Rosa, and
C Piat, and
L Capocaccia
January 1987,
The American journal of physiology,
D Alvaro, and
P Della Guardia, and
A Bini, and
A Gigliozzi, and
S Furfaro, and
T La Rosa, and
C Piat, and
L Capocaccia
January 1991,
The American journal of physiology,
D Alvaro, and
P Della Guardia, and
A Bini, and
A Gigliozzi, and
S Furfaro, and
T La Rosa, and
C Piat, and
L Capocaccia
January 1993,
Biochemical pharmacology,
D Alvaro, and
P Della Guardia, and
A Bini, and
A Gigliozzi, and
S Furfaro, and
T La Rosa, and
C Piat, and
L Capocaccia
June 1992,
The American journal of physiology,
D Alvaro, and
P Della Guardia, and
A Bini, and
A Gigliozzi, and
S Furfaro, and
T La Rosa, and
C Piat, and
L Capocaccia
January 1985,
Transactions of the Association of American Physicians,
D Alvaro, and
P Della Guardia, and
A Bini, and
A Gigliozzi, and
S Furfaro, and
T La Rosa, and
C Piat, and
L Capocaccia
June 1985,
The Journal of biological chemistry,
D Alvaro, and
P Della Guardia, and
A Bini, and
A Gigliozzi, and
S Furfaro, and
T La Rosa, and
C Piat, and
L Capocaccia
May 2001,
Hepatology research : the official journal of the Japan Society of Hepatology,
D Alvaro, and
P Della Guardia, and
A Bini, and
A Gigliozzi, and
S Furfaro, and
T La Rosa, and
C Piat, and
L Capocaccia
May 1990,
Journal of hepatology,
D Alvaro, and
P Della Guardia, and
A Bini, and
A Gigliozzi, and
S Furfaro, and
T La Rosa, and
C Piat, and
L Capocaccia
June 1997,
The American journal of physiology,
D Alvaro, and
P Della Guardia, and
A Bini, and
A Gigliozzi, and
S Furfaro, and
T La Rosa, and
C Piat, and
L Capocaccia
January 1987,
Proceedings of the Western Pharmacology Society,
