HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: 296/4/G923    most recent 90363.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Bassil, A. K. Articles by Moore, G. B. T. Search for Related Content PubMed PubMed Citation Articles by Bassil, A. K. Articles by Moore, G. B. T.

NEUROREGULATION AND MOTILITY

UDP-glucose modulates gastric function through P2Y₁₄ receptor-dependent and -independent mechanisms

Departments of ¹Gastrointestinal Research, Neurology and Gastrointestinal Centre of Excellence for Drug Discovery, Harlow, United Kingdom; ²Discovery Technology Group, GlaxoSmithKline, Harlow, United Kingdom and Philadelphia, Pennsylvania; ³Laboratory Animal Sciences, GlaxoSmithKline, Welwyn, United Kingdom; and ⁴Quantitative Expression and Genomic Histology, GlaxoSmithKline, Research Triangle Park, North Carolina, and Welwyn, United Kingdom

Submitted 4 June 2008 ; accepted in final form 14 January 2009

P2Y receptors have been reported to modulate gastrointestinal functions. The newest family member is the nucleotide-sugar receptor P2Y₁₄. P2ry14 mRNA was detected throughout the rat gut, with the highest level being in the forestomach. We investigated the role of the receptor in stomach motility using cognate agonists and knockout (KO) mice. In rat isolated forestomach, 100 µM UDP-glucose and 100 µM UDP-galactose both increased the baseline muscle tension (BMT) by 6.2 ± 0.6 and 1.6 ± 0.6 mN (P < 0.05, n = 3–4), respectively, and the amplitude of contractions during electrical field stimulation (EFS) by 3.7 ± 1.7 and 4.3 ± 2.5 mN (P < 0.05, n = 3–4), respectively. In forestomach from wild-type (WT) mice, 100 µM UDP-glucose increased the BMT by 1.0 ± 0.1 mN (P <0.05, n = 6) but this effect was lost in the KO mice (change of –0.1 ± 0.1 mN, n = 6). The 100 µM UDP-glucose also increased the contraction amplitude during EFS in this tissue from the WT animals (0.9 ± 0.4 mN, P < 0.05, n = 6) but not from the KO mice (0.0 ± 0.2 mN, n = 6). In vivo, UDP-glucose at 2,000 mg/kg ip reduced gastric emptying in rats by 49.7% (P < 0.05, n = 4–6) and in WT and KO mice by 56.1 and 66.2%, respectively (P < 0.05, n = 7–10) vs. saline-treated control animals. There was no significant difference in gastric emptying between WT and KO animals receiving either saline or D-glucose. These results demonstrate a novel function of the P2Y₁₄ receptor associated with contractility in the rodent stomach that does not lead to altered gastric emptying after receptor deletion and an ability of UDP-glucose to delay gastric emptying without involving the P2Y₁₄ receptor.

contractility; gastric emptying