1672-P: Prostaglandin D2 Stimulates GLP-1 Secretion Dose-Dependently in the Isolated Perfused Rat Colon

Introduction and Objective: Prostaglandin D2 (PGD2) promotes mucous secretion and mucosal blood flow; however, its role in intestinal hormone secretion is unclear. Our aim was to investigate the effects of PGD2 on colonic L-cell hormone secretion. Methods: Isolated rat colon was vascularly perfused using a single-pass system with a modified Krebs-Ringer bicarbonate buffer. Arterial and luminal flow were clamped at 3 mL/min and 0.150 mL/min, respectively. The colon was allowed to stabilize for 25 minutes. PGD2 was infused intravascularly. In separate experiments, (I) asapiprant (DP1 receptor antagonist) and fevipiprant (DP2 receptor antagonist) were individually co-infused with PGD2, and (II) BW 425C (DP1 receptor agonist; 100 nM) was infused intraluminally and intravascularly. KCl (50 mM) was infused as a positive control. Glucagon-like peptide-1 (GLP-1), GLP-2, and peptide YY (PYY) were measured by radioimmunoassay. Percent change from baseline was assessed by one-way ANOVA. Results: Infusion of 10 nM, and 100 nM PGD2 significantly increased secretion of GLP-1, GLP-2, and PYY (Figure 1; n=4). Asapiprant blunted the colonic GLP-1 response to PGD2 (1 μM: -36%; 10 μM: -42%, n=3). BW 245C (n=4) stimulated GLP-1 secretion from the colon when infused intravascularly (+112%; p=0.0074), but not intraluminally (p=0.97). Conclusion: PGD2 stimulates L-cell hormone secretion via basolateral DP1 receptors. Disclosure T.A. Cookson: None. J.K. Friis: None. I.M. Modvig: None. V. Abba: None. J.J. Holst: Advisory Panel; Novo Nordisk A/S. Consultant; Novo Nordisk A/S. Other Relationship; Novo Nordisk A/S. Consultant; AstraZeneca, Fractyl Health, Inc., MSD Life Science Foundation, Structure Therapeutics, Inc. S. Veedfald: None. Funding Dansk Frie Forskningsråd (3101-00127A)