| Prokineticin-1 evokes secretory and contractile activity in rat small intestine. | |
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MedLine Citation:
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PMID: 19930539 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Prokineticins 1 and 2 (PROK1 and PROK2) are so named because they contract gastrointestinal smooth muscle, yet little else is known about their role in gastrointestinal function. Therefore, we used a combination of approaches to elucidate the mechanisms by which PROK1 alters ileal contractility and secretion in rats. METHODS: RT-PCR and immunofluorescence were used to determine PROK and receptor (PK-R) mRNA levels and PK-R1 localization, respectively. Upper GI transit and fluid secretion were determined in vivo. Contractility and intestinal epithelial ion transport were assessed in isolated ileal segments. KEY RESULTS: In the gastric fundus, PROK1 mRNA is highly expressed (70-fold >PROK2 mRNA) whereas the ileum has the highest mRNA expression of its receptor. PK-R1 immunoreactivity is visualized in ileal crypt cells, and in submucosal and myenteric neurons. In ileal segments, PROK1 evokes biphasic contractile responses consisting of an early, TTX-sensitive response (EC(50) = 87.8 nmol L(-1)) followed by a late, TTX-insensitive (EC(50) = 72.4 nmol L(-1)) component that is abolished in mucosa-free preparations. Oral administration of PROK1 enhances small bowel transit (111 +/- 3% of control) and fluid secretion (340 +/- 90% of control) and in muscle-stripped ileal preparations increases short-circuit current (EC(50) = 8.2 nmol L(-1)) in a TTX-insensitive manner. The PROK1-evoked Cl- secretion is reduced by piroxicam (non-selective cyclooxygenase inhibitor), and a prostaglandin EP(4) receptor antagonist (AH23848), but not a thromboxane receptor antagonist (GR32191B). CONCLUSIONS & INFERENCES: These results demonstrate that PROK1 has oral prokinetic and secretogogue activity and that it acts on the intestinal mucosa via PK-R1 and prostaglandin receptors to mediate these effects. |
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Authors:
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P R Wade; J M Palmer; J Mabus; P R Saunders; S Prouty; K Chevalier; M G Gareau; S McKenney; P J Hornby |
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Publication Detail:
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Type: Journal Article Date: 2009-11-25 |
Journal Detail:
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Title: Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society Volume: 22 ISSN: 1365-2982 ISO Abbreviation: Neurogastroenterol. Motil. Publication Date: 2010 May |
Date Detail:
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Created Date: 2010-04-19 Completed Date: 2010-07-15 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9432572 Medline TA: Neurogastroenterol Motil Country: England |
Other Details:
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Languages: eng Pagination: e152-61 Citation Subset: IM |
Affiliation:
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Enterology Research Team, Drug Discovery, Johnson & Johnson Pharmaceutical Research and Development, LLC, Spring House, PA, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Analysis of Variance Animals Fluorescent Antibody Technique Gastrointestinal Hormones / genetics, metabolism* Gastrointestinal Transit / physiology Intestine, Small / metabolism*, secretion Male Muscle Contraction / physiology* Muscle, Smooth / metabolism* Rats Rats, Sprague-Dawley Receptors, G-Protein-Coupled / metabolism Reverse Transcriptase Polymerase Chain Reaction Vascular Endothelial Growth Factor, Endocrine-Gland-Derived / genetics, metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Gastrointestinal Hormones; 0/Receptors, G-Protein-Coupled; 0/Vascular Endothelial Growth Factor, Endocrine-Gland-Derived; 0/prokineticin 1, rat |
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