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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3 Pt 1
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pubmed:dateCreated |
1997-10-23
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pubmed:abstractText |
Cholecystokinin (CCK) receptors are found on vagal afferent fibers. In pancreatic acini, CCK receptors exist in high- and low-affinity states. The aim of this study was to identify the vagal CCK-A receptor affinity state that mediates the effect of CCK on pancreatic protein secretion. Using a rat model with a pancreatic-biliary cannula, we studied the effects of CCK-JMV-180 on exocrine pancreatic function. CCK-JMV-180 acts as an agonist on high-affinity CCK receptors and as an antagonist on low-affinity CCK receptors. Infusion of CCK-JMV-180 (22-88 micrograms.kg-1.h-1) caused dose-dependent increases in pancreatic protein secretion, which were blocked by the CCK-A receptor antagonist L-364,718. Acute vagotomy in anesthetized rats and perivagal application of capsaicin in conscious rats abolished pancreatic responses to CCK-JMV-180 at 22 and 44 micrograms.kg-1.h-1. CCK-JMV-180 did not reduce pancreatic responses to CCK octapeptide infusion at 20 and 40 pmol.kg-1.h-1. To demonstrate that endogenously released CCK also acts on high-affinity CCK-A receptors, we showed that in conscious rats intraduodenal infusion of 18% casein produced a threefold increase in protein secretion and elevated plasma CCK levels from 0.7 to 8.4 pM. Infusion of CCK-JMV-180 at 44 micrograms.kg-1.h-1 failed to inhibit pancreatic responses to casein. In separate studies, perivagal application of 1% capsaicin inhibited 95% and 90% of the pancreatic responses to casein and casein combined with intravenous CCK-JMV-180, respectively. The neurotoxic effect of capsaicin on small-diameter sensory vagal fibers was verified by immunohistochemical and retrograde tracing studies. In conclusion, we demonstrated that in contrast to their effect on satiety, which is mediated by vagal low-affinity CCK-A receptors, exogenous CCK and endogenous CCK under physiological conditions act through high-affinity CCK-A receptors to mediate pancreatic protein secretion. These findings suggest that different affinity states of the vagal CCK receptors mediate different digestive functions.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Atropine,
http://linkedlifedata.com/resource/pubmed/chemical/Benzodiazepinones,
http://linkedlifedata.com/resource/pubmed/chemical/Capsaicin,
http://linkedlifedata.com/resource/pubmed/chemical/Caseins,
http://linkedlifedata.com/resource/pubmed/chemical/Devazepide,
http://linkedlifedata.com/resource/pubmed/chemical/Hexamethonium,
http://linkedlifedata.com/resource/pubmed/chemical/Hormone Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/JMV 180,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Cholecystokinin A,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cholecystokinin,
http://linkedlifedata.com/resource/pubmed/chemical/Sincalide
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0002-9513
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
273
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
G679-85
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:9316472-Animals,
pubmed-meshheading:9316472-Atropine,
pubmed-meshheading:9316472-Benzodiazepinones,
pubmed-meshheading:9316472-Capsaicin,
pubmed-meshheading:9316472-Caseins,
pubmed-meshheading:9316472-Devazepide,
pubmed-meshheading:9316472-Duodenum,
pubmed-meshheading:9316472-Hexamethonium,
pubmed-meshheading:9316472-Hormone Antagonists,
pubmed-meshheading:9316472-Infusions, Intravenous,
pubmed-meshheading:9316472-Infusions, Parenteral,
pubmed-meshheading:9316472-Kinetics,
pubmed-meshheading:9316472-Male,
pubmed-meshheading:9316472-Pancreas,
pubmed-meshheading:9316472-Rats,
pubmed-meshheading:9316472-Rats, Sprague-Dawley,
pubmed-meshheading:9316472-Receptor, Cholecystokinin A,
pubmed-meshheading:9316472-Receptors, Cholecystokinin,
pubmed-meshheading:9316472-Sincalide,
pubmed-meshheading:9316472-Vagotomy,
pubmed-meshheading:9316472-Vagus Nerve
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pubmed:year |
1997
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pubmed:articleTitle |
High-affinity CCK-A receptors on the vagus nerve mediate CCK-stimulated pancreatic secretion in rats.
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pubmed:affiliation |
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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