CGRP antagonists and capsaicin on celiac ganglia partly prevent postoperative gastric ileus.
The role of capsaicin-sensitive pathways and CGRP in postoperative gastric ileus was investigated. Abdominal surgery was performed under enflurane anesthesia, and 5 min later, the 20-min rate of gastric emptying was measured by the phenol red method in conscious rats. Surgery inhibited gastric emptying by 76-83% compared with rats receiving anesthesia alone. Capsaicin on the celiac/mesenteric ganglia (10-21 days before) reduced gastric ileus by 33 +/- 8%, whereas perivagal capsaicin had no effect. The IV CGRP-induced inhibition of gastric emptying was completely reversed by the CGRP antagonist, CGRP(8-37) (30 micrograms, IV); CGRP(8-37) (15, 30, or 60 micrograms) or CGRP monoclonal antibody #4901 (2 mg protein) decreased the inhibition of gastric emptying by 11 +/- 7%, 51 +/- 13%, 47 +/- 3%, and 45 +/- 17%, respectively. These results indicate that CGRP and splanchnic capsaicin-sensitive afferents are involved in mediating part of the gastric ileus observed immediately after abdominal surgery.
Plourde
V
V
CURE/Digestive Disease Center, VA Wadsworth Medical Center, Los Angeles, CA.
Wong
H C
HC
Walsh
J H
JH
Raybould
H E
HE
Taché
Y
Y
D000344:Afferent Pathways / Q000187:drug effects; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors / Q000276:immunology / Q000494:pharmacology / Q000502:physiology*; D002211:Capsaicin / Q000494:pharmacology*; D005728:Ganglia, Sympathetic / Q000187:drug effects*; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D011183:Postoperative Complications / Q000517:prevention & control; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects; D013272:Stomach Diseases / Q000517:prevention & control*; D013373:Substance P / Q000037:antagonists & inhibitors; D014630:Vagus Nerve / Q000187:drug effects
D000911:Antibodies, Monoclonal; D010446:Peptide Fragments; C058636:calcitonin gene-related peptide (8-37); D013373:Substance P; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin