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, 51Cr was applied via the catheter positioned to the proximal colon. 90 min after 51Cr 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.
Nakade
Yukiomi
Y
Department of Surgery, Duke University Medical Center, Durham Veterans Affairs Medical Center, Durham, NC 27705, USA.
Tsukamoto
Kiyoshi
K
Iwa
Masahiro
M
Pappas
Theodore N
TN
Takahashi
Toku
T
D000704:Analysis of Variance; D000818:Animals; D002859:Chromium Isotopes / Q000493:pharmacokinetics; D003106:Colon / Q000187:drug effects*; D003243:Consciousness; D003346:Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D005769:Gastrointestinal Motility / Q000187:drug effects*; D052216:Glucagon-Like Peptide 1 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D009434:Neural Pathways / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014628:Vagotomy / Q000379:methods; D014630:Vagus Nerve / Q000502:physiology*
D002859:Chromium Isotopes; D010446:Peptide Fragments; C104416:astressin; C083773:exendin (9-39); D052216:Glucagon-Like Peptide 1; D003346:Corticotropin-Releasing Hormone