Diazepam-binding inhibitor mediates feedback regulation of pancreatic secretion and postprandial release of cholecystokinin

Li, Ying; Hao, Ya; Owyang, Chung

doi:10.1172/jci7204

Cited by 55 publications

(33 citation statements)

References 27 publications

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“…Given its influence on gastric motility, perhaps the transport of peptides via PepT1 by the enterocyte may initiate secretion of signaling factors that stimulate the I cell to secrete CCK. This signaling factor may be diazepam-binding inhibitor (DBI), a CCKreleasing peptide originally isolated in the rat intestinal mucosa that has been demonstrated to elicit pancreatic secretion and elevate plasma CCK levels in the rat (20) and elicit CCK secretion by the STC-1 cell (44). It would be interesting to test whether a connection exists between PepT1-transporter activity and DBI secretion by the intestinal mucosa in CCK secretion.…”

Section: G899 Protein Hydrolysate-induced Cholecystokinin Secretionmentioning

confidence: 99%

Protein hydrolysate-induced cholecystokinin secretion from enteroendocrine cells is indirectly mediated by the intestinal oligopeptide transporter PepT1

Liou

Chavez

Espero

et al. 2011

American Journal of Physiology-Gastrointestinal and Liver Physi

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Dietary protein is a major stimulant for cholecystokinin (CCK) secretion by the intestinal I cell, however, the mechanism by which protein is detected is unknown. Indirect functional evidence suggests that PepT1 may play a role in CCK-mediated changes in gastric motor function. However, it is unclear whether this oligopeptide transporter directly or indirectly activates the I cell. Using both the CCK-expressing enteroendocrine STC-1 cell and acutely isolated native I cells from CCK-enhanced green fluorescent protein (eGFP) mice, we aimed to determine whether PepT1 directly activates the enteroendocrine cell to elicit CCK secretion in response to oligopeptides. Both STC-1 cells and isolated CCK-eGFP cells expressed PepT1 transcripts. STC-1 cells were activated, as measured by ERK1/2 phosphorylation, by both peptone and the PepT1 substrate Cefaclor; however, the PepT1 inhibitor 4-aminomethyl benzoic acid (AMBA) had no effect on STC-1 cell activity. The PepT1-transportable substrate glycyl-sarcosine dose-dependently decreased gastric motility in anesthetized rats but had no affect on activation of STC-1 cells or on CCK secretion by CCK-eGFP cells. CCK secretion was significantly increased in response to peptone but not to Cefaclor, cephalexin, or Phe-Ala in CCK-eGFP cells. Taken together, the data suggest that PepT1 does not directly mediate CCK secretion in response to PepT1 specific substrates. PepT1, instead, may have an indirect role in protein sensing in the intestine.

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Section: G899 Protein Hydrolysate-induced Cholecystokinin Secretionmentioning

confidence: 99%

Protein hydrolysate-induced cholecystokinin secretion from enteroendocrine cells is indirectly mediated by the intestinal oligopeptide transporter PepT1

Liou

Chavez

Espero

et al. 2011

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…TTN and ODN are also present in many peripheral organs, including the duodenum where they activate voltage-dependent L-type calcium channels via peripheral benzodiazepine receptors in intestinal endocrine cells, resulting in the release of the gastrointestinal hormone cholecystokinin (20,21). The sequence of AcbA of Dictyostelium shows that trypsin could generate a peptide of 34 aa with 44% sequence identity to human TTN (Fig.…”

Section: Figmentioning

confidence: 99%

Peptide signaling during terminal differentiation ofDictyostelium

Anjard

Loomis

2005

Proc. Natl. Acad. Sci. U.S.A.

144

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A wide variety of mechanisms have evolved for intercellular communication in metazoans, but some of the signaling molecules were already used in their predecessors. The social amoeba, Dictyostelium discoideum, is known to use peptides to trigger sporulation within fruiting bodies, but their sequences have not been defined. We found that the peptide signal spore differentiation factor 2 (SDF-2) is processed from acyl-CoA binding protein, AcbA. The mammalian homolog of AcbA is processed to diazepam binding inhibitor that binds to the GABA A receptor in the brain and to peripheral 1,4 benzodiazepine receptors. Although Dictyostelium has neither GABAA nor peripheral-type benzodiazepine receptors, we find that both a diazepam binding inhibitor peptide and diazepam (Valium) can mimic SDF-2 in a Dictyostelium bioassay. Mutants lacking AcbA sporulate well only when developed in chimeras with WT cells. Using a yeast system we show that ligand binding to the SDF-2 receptor histidine kinase, DhkA, inhibits phosphorelay, which can account for its ability to induce rapid sporulation.receptor histidine kinase ͉ diazepam binding inhibitor ͉ triakontatetraneuropeptide ͉ octadecaneuropeptide ͉ diazepam

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“…In rats, foods rich in protein (21,29) and fats (20) are the most potent stimulants of CCK release (19). Fatty acids such as sodium oleate (SO) appear to function by direct stimulation of CCK-containing enteroendocrine cells of the gastrointestinal mucosa (3).…”

mentioning

confidence: 99%

An enteric signal regulates putative gastrointestinal presympathetic vasomotor neurons in rats

Sartor¹,

Shulkes²,

Verberne³

2006

American Journal of Physiology-Regulatory, Integrative and Comp

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Sartor, Daniela M., Arthur Shulkes, and Anthony J. M. Verberne. An enteric signal regulates putative gastrointestinal presympathetic vasomotor neurons in rats. Am J Physiol Regul Integr Comp Physiol 290: R625-R633, 2006. First published October 20, 2005 doi:10.1152/ajpregu.00639.2005.-Ingestion of a meal results in gastrointestinal (GI) hyperemia and is associated with systemic and paracrine release of a number of peptide hormones, including cholecystokinin (CCK) and 5-hydroxytryptamine (5-HT). Systemic administration of CCK octapeptide inhibits a subset of presympathetic neurons of the rostroventrolateral medulla (RVLM) that may be responsible for driving the sympathetic vasomotor tone to the GI viscera. The aim of this study was to determine whether endogenous release of CCK and/or 5-HT also inhibits CCK-sensitive RVLM neurons. The effects of intraduodenal administration of the secretagogues sodium oleate (SO) and soybean trypsin inhibitor (SBTI) on circulating levels of CCK and 5-HT were examined. In separate experiments, the discharge rates of barosensitive, medullospinal, CCK-sensitive RVLM presympathetic vasomotor neurons were recorded after rapid intraduodenal infusion of SO-SBTI or water. Alternatively, animals were pretreated with the CCK 1 receptor antagonists devazepide and lorglumide or the 5-HT 3 antagonist MDL-72222 before SO-SBTI administration. Secretagogue infusion significantly increased the level of circulating CCK, but not 5-HT. SO-SBTI significantly decreased (58%) the neuronal firing rate of CCKsensitive RVLM neurons compared with water (5%). CCK 1 receptor antagonists did not reverse SO-SBTI-induced neuronal inhibition (58%), whereas the 5-HT 3 antagonist significantly attenuated the effect (22%). This study demonstrates a functional relation between a subset of RVLM presympathetic vasomotor neurons and meal-related signals arising from the GI tract. It is likely that endogenously released 5-HT acts in a paracrine fashion on GI 5-HT 3 receptors to initiate reflex inhibition of these neurons, resulting in GI vasodilatation by withdrawal of sympathetic tone. rostroventrolateral medulla; cholecystokinin; devazepide; MDL-72222; 5-hydroxytryptamine GASTROINTESTINAL HYPEREMIA is a physiological consequence of food consumption. Gastrointestinal hormones such as cholecystokinin (CCK) have been implicated in gastrointestinal vasodilatation associated with postprandial increase in splanchnic blood flow. The involvement of the sympathetic vasomotor system in this response is poorly understood. We recently suggested that food-related signals may produce gastrointestinal vasodilatation via a reflex withdrawal of sympathetic vasomotor outflow (39,45). In healthy individuals, the sympathetic nervous system compensates for postprandial splanchnic blood pooling by activating sympathetic vasoconstrictor drive to skeletal muscle resistance vessels in response to baroreceptor unloading. In patients with cardiovascular disease associated with diabetic neuropathy or autonomic dysfunction, poor baroreflex comp...

show abstract

Diazepam-binding inhibitor mediates feedback regulation of pancreatic secretion and postprandial release of cholecystokinin

Cited by 55 publications

References 27 publications

Protein hydrolysate-induced cholecystokinin secretion from enteroendocrine cells is indirectly mediated by the intestinal oligopeptide transporter PepT1

Protein hydrolysate-induced cholecystokinin secretion from enteroendocrine cells is indirectly mediated by the intestinal oligopeptide transporter PepT1

Peptide signaling during terminal differentiation ofDictyostelium

An enteric signal regulates putative gastrointestinal presympathetic vasomotor neurons in rats

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