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

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 usi...

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Veröffentlicht in:American journal of physiology: Gastrointestinal and liver physiology 2009-04, Vol.296 (4), p.G923-G930
Hauptverfasser: Bassil, Anna K, Bourdu, Sophie, Townson, Karen A, Wheeldon, Alan, Jarvie, Emma M, Zebda, Noureddine, Abuin, Alejandro, Grau, Evelyn, Livi, George P, Punter, Lorraine, Latcham, Judith, Grimes, Angela M, Hurp, David P, Downham, Kelly M, Sanger, Gareth J, Winchester, Wendy J, Morrison, Alastair D, Moore, Gary B T
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container_end_page G930
container_issue 4
container_start_page G923
container_title American journal of physiology: Gastrointestinal and liver physiology
container_volume 296
creator Bassil, Anna K
Bourdu, Sophie
Townson, Karen A
Wheeldon, Alan
Jarvie, Emma M
Zebda, Noureddine
Abuin, Alejandro
Grau, Evelyn
Livi, George P
Punter, Lorraine
Latcham, Judith
Grimes, Angela M
Hurp, David P
Downham, Kelly M
Sanger, Gareth J
Winchester, Wendy J
Morrison, Alastair D
Moore, Gary B T
description 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 microM UDP-glucose and 100 muM UDP-galactose both increased the baseline muscle tension (BMT) by 6.2+/-0.6 and 1.6+/-0.6 mN (P
doi_str_mv 10.1152/ajpgi.90363.2008
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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 microM UDP-glucose and 100 muM 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 microM 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 microM 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. 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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 microM UDP-glucose and 100 muM 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 microM 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 microM 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.]]></abstract><cop>United States</cop><pmid>19164486</pmid><doi>10.1152/ajpgi.90363.2008</doi></addata></record>
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subjects Animals
Dose-Response Relationship, Drug
Gastric Emptying - drug effects
Gene Expression Regulation - physiology
Lac Operon - genetics
Lac Operon - physiology
Mice
Mice, Knockout
Muscle Contraction - drug effects
Muscle, Smooth - drug effects
Rats
Receptors, Purinergic P2 - genetics
Receptors, Purinergic P2 - metabolism
Receptors, Purinergic P2Y
RNA, Messenger - genetics
RNA, Messenger - metabolism
Uridine Diphosphate Galactose - pharmacology
Uridine Diphosphate Glucose - pharmacology
title UDP-glucose modulates gastric function through P2Y14 receptor-dependent and -independent mechanisms
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