Abstracts
1998 Digestive Disease Week

#975

DIFFERING EFFECTS OF A CALCITONIN GENE RELATED PEPTIDE (CGRP) RECEPTOR ANTAGONIST (RA) AND AN _-CGRP ANTIBODY (AB) ON POSTOP ILEUS. Mark E. Freeman, Guozhang Cheng, and Michael P. Hocking Department of Surgery, University of Florida, Gainesville, Florida.

Ablation of _-CGRP containing afferent neurons with the afferent neurotoxin capsaicin improves postop gastric emptying (GE) and small bowel transit (SBT). Both an _-CGRP Ab and a CGRP ra improve postop GE. However, we previously demonstrated that a CGRP ra, hCGRP8-37, did not improve postop SBT and actually blocked the beneficial effect of the neurotoxin capsaicin. While the stomach contains only _-CGRP located in afferent neurons, the small bowel additionally contains
_-CGRP within myenteric neurons. hCGRP8-37 blocks _-CGRP, but also blocks
_-CGRP. We postulated that blockade of _-CGRP within the myenteric plexus opposed the beneficial effects of _-CGRP blockade (or elimination of _-CGRP by capsaicin) on postop SBT. No selective _-CGRP antagonist exists. The purpose of this study was to test the hypothesis that a recently described selective _-CGRP Ab would not block _-CGRP, and would thus improve postop SBT and not block the beneficial effect of capsaicin. Methods: Male Sprague-Dawley rats underwent placement of duodenal catheters and were randomly assigned into one of six groups. Half of the animals were pretreated with 1% capsaicin applied to the SMA/celiac ganglion 1 week prior to study, while the remainder were treated with saline. Later, all animals received a bolus of sterile saline containing 0.1% BSA prior to standardized laparotomy followed by an infusion of 300 uL/h. The CGRP ra group received a 5 nmol bolus of hCGRP8-37, followed by an infusion of 10 nmol/h. The CGRP Ab group received 2 mg of Ab IV preoperatively, while controls received KLH Ab. Transit was measured 25 minutes postop, and was defined as the geometric center (median) of Cr51 distribution in 10 equally divided small bowel segments. Conclusion: Unlike the ra, pretreatment with a selective _-CGRP Ab improved postop SBT and did not block the beneficial effect of capsaicin. This suggests that hCGRP8-37 blocks both _ and _-CGRP, and that the two peptides have opposing effects on postop SBT.