Role of alpha- and beta-calcitonin gene-related peptide in postoperative small bowel ileus.
Ablation of a-calcitonin gene-related polypeptide (CGRP) containing neurons with the afferent neurotoxin capsaicin improves postoperative foregut transit in a rodent model. Similarly, administration of a selective alpha-CGRP antibody or hCGRP((8-37)), a CGRP receptor antagonist, improves postoperative gastric emptying. Unlike the stomach, which contains only alpha-CGRP, the small bowel additionally contains beta-CGRP. The role of the latter in postoperative small bowel transit is unknown. The purpose of this study was to evaluate the effect of an alpha-CGRP antibody and hCGRP((8-37)) on postoperative small bowel transit. Male Sprague-Dawley rats underwent placement of duodenal catheters and were randomly assigned to 1 of 11 groups. Four groups were pretreated with 1% capsaicin. One week later, all animals underwent standardized laparotomy following administration of a control antibody or the alpha-CGRP mono-clonal antibody, or during infusion of hCGRP((8-37)) at varying doses. Small bowel transit was measured 25 minutes postoperatively. The alpha-CGRP antibody sped postoperative transit when given alone or in combination with capsaicin. In contrast, animals treated with hCGRP((8-37)) showed no significant improvement in postoperative transit, and the beneficial effect of capsaicin was blocked. Unlike their similar effects on postoperative gastric emptying, we found that hCGRP((8-37)) and the alpha-CGRP antibody had differing effects on postoperative small bowel transit. The reason for this is unknown but may be related to their differing specificities for alpha- and beta-CGRP.
Freeman
M E
ME
Department of Surgery, VA Medical Center and the University of Florida, Gainesville, Florida 32610, USA.
Cheng
G
G
Hocking
M P
MP
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000276:immunology / Q000494:pharmacology / Q000502:physiology*; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D004195:Disease Models, Animal; D005772:Gastrointestinal Transit / Q000187:drug effects / Q000502:physiology*; D007415:Intestinal Obstruction / Q000209:etiology* / Q000503:physiopathology; D007421:Intestine, Small / Q000502:physiology* / Q000601:surgery; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D011183:Postoperative Complications / Q000209:etiology* / Q000503:physiopathology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
D000911:Antibodies, Monoclonal; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D010446:Peptide Fragments; C058636:calcitonin gene-related peptide (8-37); D015740:Calcitonin Gene-Related Peptide