Glucagon-like peptide-2 (GLP-2) reducesmouse gastric tone and small intestine transit, but its action onlarge intestine motility is still unknown. The purposes of the presentstudy were 1) to examine the influence of GLP-2 on spontaneousmechanical activity and on neurally evoked responses, by recordingintraluminal pressure from mouse isolated colonic segments; 2) tocharacterize GLP-2 mechanism of action; and 3) to determine thedistribution of GLP-2 receptor (GLP-2R) in the mouse colonicmuscle coat by immunohistochemistry. Exogenous GLP-2 (0.1–300 nM) induced a concentration-dependent reduction of the spontaneousmechanical activity, which was abolished by the desensitizationof GLP-2 receptor or by tetrodotoxin, a voltage-dependentNa+-channel blocker. GLP-2 inhibitory effect was not affected byNomega-nitro-L-arginine methyl ester (a nitric oxide synthase inhibitor),apamin (a blocker of small conductance Ca2+-dependent K+channels), or [Lys1,Pro2,5,Arg3,4,Tyr6]VIP7–28 (a VIP receptorantagonist), but it was prevented by atropine or pertussis toxin(PTX), a Gi/o protein inhibitor. Proximal colon responses to electricalfield stimulation were characterized by nitrergic relaxation,which was followed by cholinergic contraction. GLP-2 reducedonly the cholinergic evoked contractions. This effect was almostabolished by GLP-2 receptor desensitization or PTX. GLP-2 failedto affect the contractile responses to exogenous carbachol. GLP-2Rimmunoreactivity (IR) was detected only in the neuronal cells ofboth plexuses of the colonic muscle coat. More than 50% ofmyenteric GLP-2R-IR neurons shared the choline acetyltransferaseIR. In conclusion, the activation of GLP-2R located on cholinergicneurons may modulate negatively the colonic spontaneous andelectrically evoked contractions through inhibition of acetylcholinerelease. The effect is mediated by Gi protein.
|Numero di pagine||6|
|Rivista||AMERICAN JOURNAL OF PHYSIOLOGY: GASTROINTESTINAL AND LIVER PHYSIOLOGY|
|Stato di pubblicazione||Published - 2010|
All Science Journal Classification (ASJC) codes