Effects of Calcitonin Gene-Related Peptide on Colonic Motility and Defecation in Conscious Dogs
Although intra-arterial infusion of calcitonin gene-related peptide (CGRP) reportedly stimulates giant migrating contractions (GMCs) of the small intestine in conscious dogs, the effect of intravenous CGRP administration on colonic motility remains unclear. In the present study, we investigated the effects of intravenous CGRP on colonic motility and defecation and determined the underlying mechanism of action in conscious dogs.
Sixteen Beagle dogs weighing 11–13 kg were included. The effects of intravenous CGRP at doses of 3.33 (with various antagonists), 0.83, and 1.67 μg/kg on colonic motility and defecation were evaluated in neurally intact dogs (n = 6). For comparison, dogs with transection/re-anastomosis (T/R) between the proximal and middle segments of the colon (n = 5) and dogs with extrinsic denervation of the ileocolonic segments (n = 5) also received intravenous CGRP at 3.33 μg/kg. All dogs were equipped with strain gauge force transducers on the ileocolon for measurement of the colonic contractile activity.
Intravenous CGRP evoked GMCs and defecation in the neurally intact group; these stimulatory effects were inhibited by atropine and hexamethonium. Compared with the neurally intact group, the T/R group exhibited similar proximal colonic motility and decreased distal colonic motility after intravenous CGRP administration, whereas the extrinsic denervation group exhibited increased colonic motility overall.
Intravenous CGRP induces colonic motility and defecation through acetylcholine release in conscious dogs. The continuity of the enteric nerves plays an important role in CGRP-induced colonic contractions and defecation, while the extrinsic nerves suppress CGRP-induced colonic motility.
KeywordsColonic motility Calcitonin gene-related peptide Neurotransmitter Intrinsic nerve Extrinsic nerve
The authors thank Chikashi Shibata, MD, Division of gastroenterologic surgery, Tohoku Medical and Pharmaceutical University for reviewing this manuscript, and also Ms. Emiko Shibuya for technical assistance and the staff of Institute for Animal Experimentation, Graduate School of Medicine, Tohoku University, for assistance with animal husbandry and care.
Compliance with Ethical Standards
Grand Support and Disclosures
This study was supported by the grant-in-aid 25861170 for scientific research from Japan Society for the Promotion of Science. None of the authors has any conflict of interest to declare.
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