Characterization of the neurotrophic response to acute pancreatitis.
BACKGROUND
Interesting preliminary data on changes in the neurotrophin system in various digestive diseases have recently begun to emerge.


OBJECTIVE
To measure changes in messenger RNA (mRNA) levels of neurotrophins and to identify cell types expressing neurotrophins in the pancreas of rats with L-arginine-induced pancreatitis.


METHODS
Rats were killed at time points from 2 hours to 4 weeks after the induction of pancreatitis, and responses were measured by assay.


RESULTS
By RNase protection assay, ciliary neurotrophic factor (CNTF) mRNA expression showed a rapid response (sixfold increase over control) in the inflamed pancreas at 2 hours. The levels of mRNA expression of brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4) in the inflamed pancreas reached a peak at 1 week (2.5-fold, twofold, fourfold, and fivefold increase, respectively). By immunohistochemistry, immunoreactivity for all neurotrophins examined was observed in the islets of Langerhans in the control pancreas at all time points, but it was markedly reduced in the islets in the inflamed pancreas at 2 and 6 hours. Acinar and ductal cells, inflammatory cells, and neural elements were immunoreactive for those neurotrophins in the inflamed pancreas from 2 hours to 2 weeks.


CONCLUSIONS
The temporal and spatial expression of neurotrophins in the course of experimental pancreatitis suggests that their upregulation is a critical component of the response of the pancreas to injury in this model.
Enteric Neuromuscular Disorders and Pain Laboratory, Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Texas Medical Branch, Galveston, Texas 77555, USA.
Hiroki
H
Toma
John H
JH
Winston
Maria-Adelaide
MA
Micci
Hui
H
Li
Helen Lee
HL
Hellmich
Pankaj J
PJ
Pasricha
D000208:Acute Disease; D000818:Animals; D001120:Arginine; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics; D015870:Gene Expression; D051100:Glial Cell Line-Derived Neurotrophic Factor; D007150:Immunohistochemistry; D007515:Islets of Langerhans / Q000294:innervation / Q000503:physiopathology; D008297:Male; D009414:Nerve Growth Factors / Q000235:genetics*; D020933:Neurotrophin 3 / Q000235:genetics; D010195:Pancreatitis / Q000139:chemically induced / Q000503:physiopathology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
D019208:Brain-Derived Neurotrophic Factor; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D020933:Neurotrophin 3; D012333:RNA, Messenger; D001120:Arginine; C073922:neurotrophin 4