The Choleretic Effects of Glucagon and Secretin in the Dog

Jones, R. Scott; Geist, Richard E.; Hall, Albert D.

doi:10.1016/s0016-5085(71)80007-0

Cited by 75 publications

(14 citation statements)

References 12 publications

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“…Many studies have emphasized that factors other than the enterohepatic circulation of bile salts may play a role in regulating bile formation. Secretin may be an important stimulus to the secretion of water and electrolytes into the bile of dogs [Jones, Geist and Hall, 1971], cats [Scratcherd, 1965] and man [Konturek, Dabrowski, Adamczyk and Kulpa, 1969], but it appears to be an ineffective choleretic agent in rabbits [see Scratcherd, 1965;Kirchmayer, Tarnawski, Drozdz and Cichecka, 1972]. Similarly, we could not produce a choleresis in rabbits either by the intravenous infusion of porcine secretin, or by the intraduodenal infusion of acid.…”

Section: Discussionmentioning

confidence: 82%

“…However, the primacy of bile salt secretion in the regulation of bile flow of herbivores such as rats and rabbits has been questioned by Klaassen [1972] and Erlinger, Dhumeaux, Berthelot and Dumont [1970]. Gastrointestinal hormones, particularly secretin, may also be important in the regulation of bile formation in dogs [Jones, Geist and Hall, 1971], cats [Scratcherd, 1965] and man [Konturek, Dabrowski, Adamozyk and Kulpa, 1969]. However, it would appear from the small amount of information existing on the subject, that herbivores, at least the non-ruminant type, may be relatively insensitive to the effects of gastrointestinal hormones [Scratcherd, 1965;Shaw and Heath, 1972].…”

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confidence: 99%

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Regulation of Bile Formation in Rabbits and Guinea Pigs

Shaw

Heath

1974

Exp Physiol

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Despite interruption of the enterohepatic circulation of bile salts, bile flow in conscious rabbits and guinea pigs remained constant for several hours when saline was infused to compensate for loss of water and electrolytes in bile. Thus it appeared that biliary flow in these species is not as highly dependent on bile salt secretion as it is in dogs and man. The effects of other stimulants known to play an important role in regulating bile formation in other species were tested in rabbits and guinea pigs. Secretin, cholecystokinin-pancreozymin (CCK-PZ) and gastrin proved to be ineffective choleretics in rabbits although the doses of these exogenously-administered hormones were sufficient to siguificantly increase either pancreatic or gastric secretion. Trivial choleretic responses were recorded after administration of secretin and CCK-PZ to guinea pigs. Attempts were then made to elicit a choleresis by release of endogenous hormones. Again no changes in bile formation were recorded in rabbits although pancreatic secretion was stimulated. Bile flow in guinea pigs increased slightly, but the degree of duodenal acidification necessary to produce all of these responses to endogenous secretin release was probably unphysiological. Attempts to stimulate the release of endogenous CCK-PZ by infusing peptone were unsuccessful. It was concluded that if these herbivores do elaborate secretin and CCK-PZ, the factors responsible for their release may differ from those in other species. The present findings provide further evidence that the control of bile formation in rabbits and guinea pigs differs from that in other species, and it is possible that these differences could be related to the temporal pattern of their eating habits.According to Sperber [1965], bile secretion in many species is mainly due to active secretion of bile salts into the canaliculi and the subsequent osmotic flow of water. However, the primacy of bile salt secretion in the regulation of bile flow of herbivores such as rats and rabbits has been questioned by Klaassen [1972] and Erlinger, Dhumeaux, Berthelot and Dumont [1970]. Gastrointestinal hormones, particularly secretin, may also be important in the regulation of bile formation in dogs [Jones, Geist and Hall, 1971], cats [Scratcherd, 1965] and man [Konturek, Dabrowski, Adamozyk and Kulpa, 1969]. However, it would appear from the small amount of information existing on the subject, that herbivores, at least the non-ruminant type, may be relatively insensitive to the effects of gastrointestinal hormones [Scratcherd, 1965;Shaw and Heath, 1972]. It has been suggested that the failure of secretin to act as a choleretic agent in rabbits may be associated with the very high spontaneous rate of bile formation in this species [Scratcherd, 1965].The present study was designed to provide more information on the regulation of bile formation in conscious rabbits and guinea pigs, two species which have the highest rates of bile formation known.

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Section: Discussionmentioning

confidence: 82%

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confidence: 99%

Regulation of Bile Formation in Rabbits and Guinea Pigs

Shaw

Heath

1974

Exp Physiol

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“…Most of the investigative effort, however, has focused on the effect of glucagon, a known stimulator of adenylate cyclase. Several reports (10, 42, 93,98,103,109,143) indicate that glucagon is a moderately effective choleretic in man and dogs, but few directly address the question of whether this fl ow arises in the canaliculi or the ducts-an issue of special significance in view of the structural similarity between glucagon and secretin and a recent report (109) that secretin increases the biliary excretion of cAMP in man and baboons, though not in dogs. Barnhart (10) fo und equivalent increases in erythritol clearance and bile fl ow during glucagon choleresis in anesthetized dogs, but Russell (143), who used conscious dogs could not distinguish the changes in erythritol clearance during glucagon choleresis from those produced by secretin, although the choleresis produced by taurocholate was easily identified on this basis.…”

Section: Mechanisms Of Canalicular Fluid Productionmentioning

confidence: 99%

Mechanisms of Hepatic Bile Formation

Forker¹

1977

Annu. Rev. Physiol.

163

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It should be evident from this review of recent investigations that we are still very far from a consistent description of bile formation, much less a satisfactory understanding. Nevertheless certain broad conclusions emerge. Four distinct kinds of active solute transport can be identified, and because bile always has nearly the same osmotic pressure as plasma, each of them is a determinant of bile flow. 1. Concentrative transport of water-soluble organic constituents, of which bile acids are quantitatively most important, occurs in the canaliculi accompanied by the passive flow of water and inorganic electrolytes. Owing to micelle formation the osmotic force for this flow is largely attributable to Na+ ions that accompany the bile acids anions. 2. The canalicular flow obligated by the excretion of bile acids is supplemented by the entry of additional fluid, the so-called bile acid-independent canalicular fraction. Because no organic component has been identified to account for this phenomenon, the active transport of one or more inorganic ions is probably responsible. The limited evidence available at present suggests that Na+ ions is the most likely candidate. 3. The extralobular biliary epithelium can modify the flow and composition of bile by the reabsorption of inorganic ions--a process which resembles reabsorption from the gallbladder in the sense that bile in the lumen remains iso-osmotic with plasma while bile acids and the other organic constituents are concentrated. 4. Under the influence of secretin, and to a lesser degree other intestinal hormones, the ducts or ductules can secrete additional fluid in which HCO3- is concentrated with respect to plasma. A fifth component of bile is generated by the canalicular excretion of phospholipid and cholesterol, but these are insoluble in water and are incorporated into micelles, and, therefore exert no osmotic force. The existence of these processes is inferred from studies of many different species, and it should be emphasized that the picture is a composite one. For example, distal fluid reabsorption has been convincingly demonstrated only in dogs and monkeys, and secretin is not a choleretic in rats or rabbits. It should also be clear that the actual mechanisms of solute transport remain poorly defined. Thus the term active transport in the present context should be thought of in its general thermodynamic sense rather than as denoting any particular transport mechanism. For the future, the most pressing problems are methodologic. To mention only three that seem especially important: ways must be found to sample bile closer to its origin; the proper interpretation of studies with isolated liver cell membranes will require unambiguous methods to certify their source; and descriptions of transport kinetics must somehow be refined to reflect the effective intracellular concentration of solutes as well as their distribution within the liver lobule.

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“…Jones et al [54] reported that when glucagon was given to dogs there was an increased flow of bile. Dyck and Janowitz [55] reported that in T-tube patients the flow of bile increased following treatment with glucagon.…”

Section: Discussionmentioning

confidence: 99%

Gastrointestinal radiography with glucagon

Miller

Chernish

Brunelle

1979

Gastrointest Radiol

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This report summarizes the results of nine diagnostic radiographic studies done double blind crossover comparing glucagon to placebo and to anticholinergic drugs in volunteers. In seven studies the subjects were administered drug intramuscularly and in two studies intravenously. There were five diagnostic studies of the upper gastrointestinal tract, one for esophageal varices and three of the colon. The results indicate that glucagon can be given intramuscularly and intravenously. When given intravenously it has a rapid onset and predictable length of action depending on the dose given. Reports of side effects were few consisting primarily of nausea and or vomiting. These results indicate that glucagon is the drug of choice for hypotonic diagnostic examinations.

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The Choleretic Effects of Glucagon and Secretin in the Dog

Cited by 75 publications

References 12 publications

Regulation of Bile Formation in Rabbits and Guinea Pigs

Regulation of Bile Formation in Rabbits and Guinea Pigs

Mechanisms of Hepatic Bile Formation

Gastrointestinal radiography with glucagon

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