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KMID : 0360419820180010043
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Korean Journal of Pharmacology
1982 Volume.18 No. 1 p.43 ~ p.54
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Study on the Relationship between Biliary Secretion and Cyclic Nucleotides
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Abstract
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Bile formation is a complex process comprised of three separate physiologic mechanism operating at two anatomical sites. At present time, it was known that at least two processes are responsible for total canalicular secretion at the bile canaliculus. One of the processes is bile salt-dependent secretion (BSDS) hypothesis that the active transport of bile salts from plasma to bile provided a primary stimulus for bile formation: the osmotic effect of actively transported bile acid was responsible for the movement of water and ions into bile. The other process is bile salt-independent secretion (ESIS), which is unrelated to bile salt secretion at the canaliculus and which may involve the active transport of sodium. The third process for bile formation involves the biliary ductal epithelium. Secretin-stimulated bile characteristically contained bicarbonate in high concentration. Therefore, it was suggested that secretin stimulated water and bicarbonate secretion from the biliary ductules.
One the other hand, it was found that a large amounts of cAMP was present in canine bile but no apparent relationship between bile salt secretion and cAMP content in dog bile. However, bile flow studies in human have demonstrated that secretin and glucagon increase bile cAMP secretion as does secretin in baboons. Secretin increases baboon bile duct mucosal cAMP levels in addition to bile cAMP levels suggesting that in that species secretin-stimulated bile flow may be cAMP mediated. It has been postulated that glucagon and theophylline which increase the bile salt-independent secretion in dogs might act through an increase in liver cAMP content. In a few studies, the possible role of cAMP on bile formation has been tested by administration of an exogenous derivative of cAMP, dibutyryl cAMP. In the rat, DB CAMP did not modify bile flow, but injection of DB cAMP in the dog promoted an increase in the bile salt-independent secretion. Because of these contradictory results, this study was carried out to examine the relationship between cyclic nucleotides and bile flow due to various bile salts as well as secretin or theophylline.
Experiments were performed in rabbits with anesthesia produced by the injection of seconal(30mg/kg). Rabbits had the cystic duct ligated and the proximal end of the divided common duct cannulated with an appropriately sized polyethylene catheter. A similar catheter was placed into the inferior vena cava for administration of drugs. Bile was collected for determination of cyclic nucleotides and total cholate in 15 min. intervals for a few hours.
The results are summerized as followings.
1) Administrations of taurocholic acid or chenodeoxycholic acid increased significantly the concentrations of cAMP and cGMP in bile of rabbits.
2) Concentration of cAMP in bile during the continuous infusion of ursodeoxycholic acid was remarkedly increased in accordance with the increase of bile flow, while on the contrary concentration of cGMP in bile was decreased significantly.
3) Dehydrocholic acid and deoxycholic acid significantly increased bile flow, total cholate output and cyclic nucleotides in bile.
4) Only cAMP concentration in bile was significantly increaesd from control value by secretin, while theophylline increased cAMP as well as cGMP in rabbit bile.
5) In addition, the administration of secretin to taurocholic acid-stimulated bile flow increased cAMP while theophylline produced the increases of cAMP and cGMP in bile.
6) The administration of insulin to taurocholic acid-stimulated bile flow decreased cAMP concentration, while on the contrary cGMP was remarkedly increased in rabbit bile.
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