Multiple Actions of Secretin in the Human Body

Lam, Ian P. Y.; Siu, Francis K.Y.; Chu, Jessica; Chow, Billy K. C.

doi:10.1016/s0074-7696(07)65004-9

Cited by 28 publications

(28 citation statements)

References 178 publications

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“…39 As expected, we show that secretin stimulated an increase in intracellular cAMP levels in normal human cholangiocytes, which is similar to findings in other human cell types and in cholangiocytes from animal models. 6,9,14,39 However, in the cholangiocarcinoma cell lines that were tested, we found that secretin stimulates a dose-dependent decrease in proliferation, which was also confirmed by FACS analysis of the cell cycle. This finding was in direct contrast to those in normal human cholangiocytes and suggested that deregulation of intracellular signaling downstream of SCTR might be liable for the differential effects observed.…”

Section: Cancer Cell Biologysupporting

confidence: 59%

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Secretin inhibits cholangiocarcinoma growth via dysregulation of the cAMP‐dependent signaling mechanisms of secretin receptor

Onori

Wise

Gaudio

et al. 2010

Intl Journal of Cancer

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Secretin plays a key role in the regulation of normal cholangiocyte physiology via secretin receptor (SCTR). SCTR expression is upregulated during extrahepatic cholestasis induced by bile duct ligation and closely associated with cholangiocyte proliferative responses. Although well studied in normal cholangiocytes, the role of secretin and the expression of SCTR in the regulation of cholangiocarcinoma proliferation are unknown. In vitro, secretin (10 27 M) displayed differential effects on normal cholangiocyte [H-69 and human intrahepatic biliary epithelial cell line (HIBEpiC)] and cholangiocarcinoma (Mz-ChA-1, HuH-28, TFK-1, SG231, CCLP1 and HuCC-T1) cell lines as such secretin is mitogenic for normal cholangiocytes and antiproliferative for cholangiocarcinoma. As expected in normal cholangiocytes (HIBEpiC), secretin increased intracellular cyclic adenosine monophosphate (cAMP) levels. However, the effect of secretin on intracellular cAMP levels was suppressed in MzChA-1 cells. Secretin-stimulated intracellular cAMP levels in Mz-ChA-1 were restored by pretreatment with pertussis toxin, suggesting that the receptor coupled to Ga i rather than Ga s . SCTR expression was found to be downregulated in 4 of the 6 cholangiocarcinoma cell lines evaluated and in human cholangiocarcinoma biopsy samples. In vivo, secretin significantly inhibited the tumor size and more than doubled tumor latency, which was associated with a decrease in proliferating cell nuclear antigen and an increase in cleaved-caspase 3 expression levels. Our results demonstrate that secretin and/or the modulation of SCTR expression might have potential as a therapeutic tool in the treatment of cholangiocarcinoma.Cholangiocytes are simple epithelia, which line the intrahepatic and extrahepatic ducts and are the target of chronic cholestatic liver diseases, that are characterized biliary inflammation and by the dysregulation of the balance between cell growth and apoptosis.

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Section: Cancer Cell Biologysupporting

confidence: 59%

“…6 Secretin receptors (SCTR) belong to the family of G-protein-coupled receptors, 7 which signal through the activation of adenylyl cyclase and protein kinase A (PKA).…”

mentioning

confidence: 99%

Secretin inhibits cholangiocarcinoma growth via dysregulation of the cAMP‐dependent signaling mechanisms of secretin receptor

Onori

Wise

Gaudio

et al. 2010

Intl Journal of Cancer

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“…Secretin, a 27-amino acid peptide (molecular weight: 3055.5), is released by the duodenum in response to gastric acid and digested products of fat and protein (7,11,25). Plasma concentrations of secretin in humans, rats, and dogs are in the picomolar or low nanomolar range both at baseline and following maximal stimulation after a meal (8,16,23).…”

Section: Discussionmentioning

confidence: 99%

“…Secretin and its receptor are also expressed in extra-gastrointestinal organs including the kidney, central nervous system, cardiovascular system, and lung (7,11,25). In the kidney, the function of secretin and the location of the SCTR resemble those of vasopressin and the V2 receptor.…”

Section: Discussionmentioning

confidence: 99%

Insignificant effect of secretin in rodent models of polycystic kidney and liver disease

Wang

Ward

et al. 2012

American Journal of Physiology-Renal Physiology

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mice; and the impact of a nonfunctional secretin receptor on disease development in Pkd2 Ϫ/WS25 :SCTR Ϫ/Ϫ double mutants. Renal and hepatic secretin and secretin receptor mRNA and plasma secretin were increased in both models, and secretin receptor protein was increased in the kidneys and liver of Pkd2 Ϫ/WS25 mice. However, exogenous secretin administered subcutaneously via osmotic pumps had minimal or negligible effects and the absence of a functional secretin receptor had no influence on the severity of PKD or PLD.

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“…The principle action of secretin is to stimulate bicarbonate secretion to neutralize gastric acid in the duodenum (37,62,111).…”

Section: Actions Of Secretinmentioning

confidence: 99%

Secretin

The Pancreapedia: Exocrine Pancreas Knowledge Base

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Secretin is one of the "classical" gastrointestinal hormones and in fact was the first peptide hormone identified. The mature hormone is a 27 amino acid peptide produced and secreted by a specific type of enteroendocrine cell, the S cell which is of the open type with its apical surface exposed to luminal content. Secretin is packaged into granules and released across the basolateral membrane into the blood in response to acid in the duodenum when the pH falls below 4.5; it is also released in response to fatty acids but without a response to glucose or amino acids. Basal and stimulated concentrations are low normally in the 1-10 pM range. The principal action of secretin is to stimulate bicarbonate secretion by pancreatic and biliary ducts and duodenal Brunner's glands into the lumen such that acid in the duodenum will be neutralized. Secretin also acts to potentiate CCK action on acinar cells, to inhibit gastric acid secretion and to inhibit gastric emptying. Secretin also has actions in the brain. At the cellular level the action of secretin is primarily mediated by cAMP which is increased in response to activation of secretin receptors.

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Multiple Actions of Secretin in the Human Body

Cited by 28 publications

References 178 publications

Secretin inhibits cholangiocarcinoma growth via dysregulation of the cAMP‐dependent signaling mechanisms of secretin receptor

Secretin inhibits cholangiocarcinoma growth via dysregulation of the cAMP‐dependent signaling mechanisms of secretin receptor

Insignificant effect of secretin in rodent models of polycystic kidney and liver disease

Secretin

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