Secretin stimulates bile ductular secretory activity through the cAMP system.
Although convincing evidence has been obtained to support a ductular origin of secretin choleresis, the precise mechanism of the choleretic effect of the hormone is poorly understood. The present studies were carried out to 1) further clarify the anatomic site at which secretin stimulates bile flow and 2) establish the signal transduction system underlying this effect. To this end, parenchymal and nonparenchymal liver cells, the latter enriched in bile duct cells, were isolated from rats with ductular cell hyperplasia, and the effect of secretin on intracellular formation of both adenosine 3',5'-cyclic monophosphate (cAMP) and inositol phosphates (IPs) was compared with that observed with glucagon and [Tyr10,13,Phe22,Trp25]secretin (SG-secretin). In the pancreas, secretin stimulates both messenger systems, while SG-secretin activates only the cAMP cascade. In isolated hepatocytes, both secretin and SG-secretin failed to increase formation of cAMP and IPs, which were instead activated by glucagon. In isolated bile duct cells, secretin induced formation of both cAMP and IPs, while SG-secretin stimulated solely the cAMP system, as in the pancreas. Glucagon did not stimulate either messenger system in this cell preparation. In vivo, both secretin and SG-secretin stimulated a bicarbonate-rich fluid in rats with bile ductular cell hyperplasia and in normal guinea pigs, which was demonstrated to originate at the distal biliary epithelium. These findings support the existing view that glucagon stimulates canalicular bile flow, while secretin increases secretory activity at the bile ductules and/or ducts. More importantly, they indicate that stimulation of ductular secretory activity by secretin is mediated by the cAMP system and does not involve the IP signal transduction pathway.
Lenzen
R
R
Department of Medicine, Heinrich-Heine-University, Dusseldorf, Federal Republic of Germany.
Alpini
G
G
Tavoloni
N
N
D000818:Animals; D001646:Bile / Q000502:physiology; D001652:Bile Ducts / Q000166:cytology / Q000378:metabolism*; D001659:Biliary Tract / Q000378:metabolism; D001786:Blood Glucose / Q000032:analysis; D002469:Cell Separation; D000242:Cyclic AMP / Q000096:biosynthesis / Q000502:physiology*; D005934:Glucagon / Q000494:pharmacology; D007295:Inositol Phosphates / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012633:Secretin / Q000494:pharmacology*
D001786:Blood Glucose; D007295:Inositol Phosphates; D012633:Secretin; D005934:Glucagon; D000242:Cyclic AMP