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

Anna K. Bassil, Sophie Bourdu, Karen A. Townson, Alan Wheeldon, Emma M. Jarvie, Noureddine Zebda, Alejandro Abuin, Evelyn Grau, George P. Livi, Lorraine Punter, Judith Latcham, Angela M. Grimes (+6 others)
2009 American Journal of Physiology - Gastrointestinal and Liver Physiology  
Grimes AM, Hurp DP, Downham KM, Sanger GJ, Winchester WJ, Morrison AD, Moore GB. UDP-glucose modulates gastric function through P2Y 14 receptor-dependent and -independent mechanisms. tors have been reported to modulate gastrointestinal functions. The newest family member is the nucleotide-sugar receptor P2Y 14. 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
more » ... gnate agonists and knockout (KO) mice. In rat isolated forestomach, 100 M UDP-glucose and 100 M UDP-galactose both increased the baseline muscle tension (BMT) by 6.2 Ϯ 0.6 and 1.6 Ϯ 0.6 mN (P Ͻ 0.05, n ϭ 3-4), respectively, and the amplitude of contractions during electrical field stimulation (EFS) by 3.7 Ϯ 1.7 and 4.3 Ϯ 2.5 mN (P Ͻ 0.05, n ϭ 3-4), respectively. In forestomach from wild-type (WT) mice, 100 M UDP-glucose increased the BMT by 1.0 Ϯ 0.1 mN (P Ͻ0.05, n ϭ 6) but this effect was lost in the KO mice (change of Ϫ0.1 Ϯ 0.1 mN, n ϭ 6). The 100 M UDP-glucose also increased the contraction amplitude during EFS in this tissue from the WT animals (0.9 Ϯ 0.4 mN, P Ͻ 0.05, n ϭ 6) but not from the KO mice (0.0 Ϯ 0.2 mN, n ϭ 6). In vivo, UDP-glucose at 2,000 mg/kg ip reduced gastric emptying in rats by 49.7% (P Ͻ 0.05, n ϭ 4 -6) and in WT and KO mice by 56.1 and 66.2%, respectively (P Ͻ 0.05, n ϭ 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
doi:10.1152/ajpgi.90363.2008 pmid:19164486 fatcat:og4pqis36rflvoxyar6b7iudby