Gut responses
Subtitle: glucagon-like peptide-2 and inflammation: Nitric oxide and lower esophageal sphincter.
Published: 2005
Language: eng
Number of pages: 211
Description: Part I. GLUCAGON-LIKE PEPTIDE-2 (GLP-2) AND INFLAMMATION: GLP-2 is an intestinal hormone that enhances bowel growth and reduces severity of colonic injury in dextran sulfate sodium (DSS)-induced colitis in mice. In humans, ulcerative colitis (UC) is normally treated with aminosalicylates (ASAs) and corticosteroids (CSs) to reduce inflammation. This study addressed in a DSS mouse model whether GLP-2 interacts with therapeutic agents commonly used to treat UC. The results have shown that GLP-2 has the ability to protect colonic mucosal architecture, and is effective when given in combination with ASA, but not with CS. The findings point to a novel approach for the treatment of patients with UC.  Part II. MOTOR EFFECTS OF GLP-2 IN THE LOWER ESOPAHAGEAL SPHINCTER (LES): GLP-2 decreases gastrointestinal motility. This study in LES muscle strips has shown that the inhibitory effect of GLP-2 in the LES occurred through diminution of the cholinergic neural influence, without an effect on the muscle or nitric oxide (NO) release. Part III. NO AND LES: The LES comprises a circular component exhibiting spontaneous tone that is relaxed by NO, and a low tone sling muscle that contracts vigorously to cholinergic stimulation. There is also a difference in the relative importance of different membrane ion channels, including a number of K+ channels. The studies were directed to the influence of NO on the LES sling and circular muscles. More specifically, the studies addressed the presence of regional differences in the effect of NO on (i) muscle contractile properties and (ii) the large conductance Ca2+-activated K+ channel (BKCa) channel. The cat, which has an esophagus similar to human, was used as the experimental model. Electrophysiological recordings on isolated muscle cells, and muscle strip studies were performed. The results have shown that (i) the sling muscle has limited NO-mediated inhibition to potentially augment or replace sling relaxation effected by switching off its cholinergic excitation; and (ii) the marked responsiveness of the circular muscle BKCa channel to NO could facilitate the relaxation of its elevated intrinsic resting tone. Differences within the LES sling and circular muscles could provide new directions for therapy of LES disorders.
Notes: Source: Dissertation Abstracts International, Volume: 66-10, Section: B, page: 5171.

Thesis (Ph.D.)--University of Toronto, 2005.

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