Role of alpha- and beta-calcitonin gene-related peptide in postoperative small bowel ileus

Ablation of alpha-calcitonin gene-related polypeptide (CGRP) containing neu rons with the afferent neurotoxin capsaicin improves postoperative foregut transit in a rodent model. Similarly, administration of a selective alpha-C GRP antibody or hCGRP((8-37)), a CGRP receptor antagonist, improves postope rative gastric emptying. Unlike the stomach, which contains only alpha-CGRP , the small bowel additionally contains beta-CGRP. The role of the latter i n postoperative small bowel transit is unknown. The purpose of this study w as to evaluate the effect of an alpha-CGRP antibody and hCGRP((8-37)) on po stoperative small bowel transit. Male Sprague-Dawley rats underwent placeme nt of duodenal catheters and were randomly assigned to 1 of 11 groups. Four groups were pretreated with 1% capsaicin. One week later, all animals unde rwent standardized laparotomy following administration of a control antibod y or the alpha-CGRP monoclonal antibody or during infusion of hCGRP((8-37)) at varying doses. Small bowel transit was measured 25 minutes postoperativ ely. 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 be neficial effect of capsaicin was blocked. Unlike their similar effects on p ostoperative gastric emptying, we found that hCGRP((8-37)), and the alpha-C GRP antibody had differing effects on postoperative small bowel transit. Th e reason for this is unknown but may be related to their differing specific ities for alpha- and beta-CGRP.