Glucagon like peptide-1 accelerates colonic transit via central CRF and peripheral vagal pathways in conscious rats

Glucagon like peptide-1 (7-36) (GLP-1), one of the gastrointestinal (GI) regulatory peptide, is known to act as a stress related brain neurotransmitter mediating GI function. Central administration of GLP-1 inhibits gastric emptying. However, little is known about the effect of central GLP-1 on colonic transit. Effects and mechanism of GLP-1 on colonic transit were investigated in conscious rats. Immediately after intracerebroventricular (icv)-injection of GLP-1, Cr-51 was applied via the catheter positioned to the proximal colon. 90 min after Cr-51 injection, rats were euthanized and the colon was removed and divided into 10 equal segments. The radioactivity of each segment was counted and the geometric center (GC) was calculated. Icv-injection of GLP-1 (0.3-3 nmol) dose-dependently accelerated colonic transit [GC:4.4 +/- 0.2 in controls, 7.8 +/- 0.5 in GLP-1 (3 nmol)]. In contrast, intraperitoneal (ip)-injection of GLP-1 (3 nmol) did not modify colonic transit. Icv-injection of GLP-1 (3 nmol)-induced acceleration of colonic transit was attenuated by vagotomy, atropine and hexamethonium, but not by guanethidine. Icv-injection of GLP-1 (3 nmol)-induced acceleration of colonic transit was abolished by corticotropin releasing factor (CRF) antagonist, astressin. Restraint stress-induced acceleration of colonic transit was abolished by a selective GLP-1 receptor antagonist, exendin. These results indicate that the endogenous GLP-1 is involved in mediating stress-induced alteration of colonic transit via a central CRF and peripheral cholinergic pathways in rats. (c) 2006 Elsevier B.V. All rights reserved.