Exogenous glucagon-like peptide 1 reduces contractions in human colon circular muscle.
Glucagon-like peptide 1 (GLP1) is a naturally occurring peptide secreted by intestinal L-cells. Though its primary function is to serve as an incretin, GLP1 reduces gastrointestinal motility. However, only a handful of animal studies have specifically evaluated the influence of GLP1 on colonic motility. Consequently, the aims of this study were to investigate the effects induced by exogenous GLP1, to analyze the mechanism of action, and to verify the presence of GLP1 receptors (GLP1Rs) in human colon circular muscular strips. Organ bath technique, RT-PCR, western blotting, and immunofluorescence were used. In human colon, exogenous GLP1 reduced, in a concentration-dependent manner, the amplitude of the spontaneous contractions without affecting the frequency and the resting basal tone. This inhibitory effect was significantly reduced by exendin (9-39), a GLP1R antagonist, which per se significantly increased the spontaneous mechanical activity. Moreover, it was abolished by tetrodotoxin, a neural blocker, or Nω-nitro-l-arginine - a blocker of neuronal nitric oxide synthase (nNOS). The biomolecular analysis revealed a genic and protein expression of the GLP1R in the human colon. The double-labeling experiments with anti-neurofilament or anti-nNOS showed, for the first time, that immunoreactivity for the GLP1R was expressed in nitrergic neurons of the myenteric plexus. In conclusion, the results of this study suggest that GLP1R is expressed in the human colon and, once activated by exogenous GLP1, mediates an inhibitory effect on large intestine motility through NO neural release.
Laboratorio di Fisiologia Generale, Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Università di Palermo, Viale delle Scienze, 90128 Palermo, Italy Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT), Palermo, Italy.
Antonella
A
Amato
Sara
S
Baldassano
Rosa
R
Liotta
Rosa
R
Serio
Flavia
F
Mulè
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003106:Colon / Q000502:physiology*; D015536:Down-Regulation; D005260:Female; D005769:Gastrointestinal Motility; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction; D009132:Muscles / Q000502:physiology*; D018027:Receptors, Glucagon / Q000235:genetics / Q000378:metabolism
C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D018027:Receptors, Glucagon; D052216:Glucagon-Like Peptide 1
GLP-1 receptor expression; colonic motility; intestinal peptides; nitric oxide