Calcitonin gene-related peptide can attenuate or augment pancreatic damagein caerulein-induced pancreatitis in rats

We have recently shown that treatment with calcitonin gene-related peptide (CGRP) before and during induction of acute pancreatitis exhibits a protect ive effect against pancreatic damage evoked by overdose of caerulein. Studi es in the stomach have shown that administration of CGRP exhibits dual acti on on gastric mucosa, CGRP administration before induction of gastric lesio ns, protects gastric mucosa against damage, whereas treatment with this pep tide after development of gastric ulcer exacerbates mucosal injury. These o bservations prompt us to determine the influence of CGRP administrated befo re and after induction of pancreatitis on development and evolution of panc reatic tissue damage. Methods: Acute pancreatitis was induced by s.c. infus ion of caerulein (10 mu g/kg/h) for 5 h. CGRP was administrated (10 mu g/kg s.c. per dose) 30 min prior to caerulein infusion and 3 h later during cae rulein infusion or at the time 1 h, 4 h and 7 h after the end of caerulein infusion. Rats were sacrificed at the time 0 h, 3 h or 9 h after cessation of caerulein administration. The pancreatic blood flow (PBF), plasma activi ty of amylase, plasma interleukin-lp concentration, cell proliferation, bio chemical and morphological signs of pancreatitis were examined. Results: Ca erulein-induced pancreatitis (CIP) led to 42% decrease in DNA synthesis, 30 % inhibition of PBF, as well as, a significant Increase in pancreatic weigh t, plasma amylase activity, plasma interleukin-lp concentration, and develo pment of the histological signs of pancreatic damage (edema, leukocyte infi ltration and vacuolization). Treatment with CGRP prior and during induction of CIP attenuated the pancreatic damage what was manifested by partial rev ersion of the drop in DNA synthesis (40.9+1.7 v. 34.2+2.0 dpm/mu g DNA) and PBF (83+3% v. 70+3%). Increases in pancreatic weight and plasma interleuki n-lp were reduced. Morphology showed improvement of pancreatic integrity. A dministration of CGRP after induction of CIP aggravated pancreatic damage w hat was manifested by additional decrease in PBF and DNA synthesis. Also pa ncreatic weight as well as histological signs of pancreatic damage were inc reased. Conclusions: (1) Administration of CGRP before and during induction of pancreatitis protects pancreas against pancreatic damage. (2) Treatment with CGRP after development of CIP aggravates pancreatic damage.