Mechanism of glucagon choleresis in guinea pigs

R. Lenzen, Victor J Hruby, N. Tavoloni

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

The present studies were carried out to clarify the mechanism of glucagon choleresis in guinea pigs. At the infusion rate of 1.4 nmol·min-1·kg-1, glucagon increased bile flow from 206.6 ± 14.3 to 302.6 ± 35.0 μl·min-1·kg-1 and bicarbonate biliary concentration from 63.7 ± 4.2 to 75.5 ± 5.9 meq/l. Measurements of bile acid excretion in bile, the biliary tree volume, and of the hormone choleretic effect in guinea pigs with proliferated bile ductules/ducts induced by α-naphthylisothiocyanate feeding indicated that glucagon, unlike secretin, stimulated canalicular bile flow. Inhibition of prostaglandin synthesis by indomethacin administration (5 mg·kg-1·h-1) did not modify the choleretic effect of glucagon, and infusion of a glucagon analogue (TH-glucagon, 1.4 nmol·min-1·kg-1), which did not increase hepatic formation of adenosine 3'5'-cyclic monophosphate (cAMP), failed to stimulate bile flow. Like the parent hormone, however, TH-glucagon augmented plasma glucose levels and stimulated formation of inositol phosphates. Colchicine pretreatment (0.5 mg/kg ip) almost entirely prevented the choleretic effect of glucagon but did not modify spontaneous and bile acid-induced bile flow and the stimulatory effect of the hormone on glucose release and on hepatic formation of cAMP and inositol phosphates. Finally, glucagon produced a large increase in the biliary entry of horseradish peroxidase, even though this effect was transient and was not coupled to the increase in bile flow. These results indicate that glucagon choleresis in the guinea pig is not secondary to prostaglandin release, is canalicular in origin, involves bicarbonate secretion, is mediated by cAMP, and requires an intact microtubular system.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume259
Issue number5 22-5
StatePublished - 1990
Externally publishedYes

Fingerprint

Glucagon
Guinea Pigs
Bile
Cholagogues and Choleretics
Inositol Phosphates
Hormones
Bicarbonates
Bile Acids and Salts
Prostaglandins
Glucose
Secretin
Liver
Colchicine
Biliary Tract
Horseradish Peroxidase
Bile Ducts
Indomethacin
Adenosine

Keywords

  • Adenosine 3'5'-cyclic monophosphate
  • Colchicine
  • Horseradish peroxidase
  • Microtubular system
  • Phosphoinositides

ASJC Scopus subject areas

  • Physiology
  • Gastroenterology

Cite this

Mechanism of glucagon choleresis in guinea pigs. / Lenzen, R.; Hruby, Victor J; Tavoloni, N.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 259, No. 5 22-5, 1990.

Research output: Contribution to journalArticle

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