Carbachol induces TGF-alpha expression and colonic epithelial cell proliferation in sensory-desensitised rats.
OBJECTIVE
Signals for the expression of the peptide growth factors epidermal growth factor and transforming growth factor-alpha (TGFalpha) in the gastrointestinal mucosa are largely unknown. We have shown earlier that extrinsic afferents in the gastrointestinal tract induce TGFalpha expression in colonic mucosa via the deliberation of neurotransmitters substance P and calcitonin gene-related peptide. The aim of our present study was to determine the effects of carbachol on mucosal TGFalpha expression and epithelial cell proliferation in vivo.


METHODS
Rats were divided in three groups. Group 1 was treated with vehicle only, group 2 received one single subcutaneous injection of 250 microg/kg of carbachol and animals in group 3 were sensory-desensitised prior to the injection of 250 microg/kg carbachol. TGFalpha expression and epithelial cell proliferation was evaluated by polymerase chain reaction, Western blot analysis and bromodeoxyuridine staining.


RESULTS
Carbachol induced a significant increase in mucosal epithelial cell proliferation and TGFalpha expression. Sensory desensitisation did neither abolish the increased TGFalpha expression nor the increase in epithelial cell proliferation.


CONCLUSIONS
Parasympathetic pathways are involved in the control of TGFalpha expression in gastrointestinal mucosa as well as in epithelial cell proliferation.
Bulut
Kerem
K
Department of Internal Medicine I, St. Josef Hospital, Ruhr-University of Bochum, Bochum, Germany.
Felderbauer
Peter
P
Hoeck
Karoline
K
Schmidt
Wolfgang E
WE
Hoffmann
Peter
P
D000818:Animals; D015153:Blotting, Western; D001973:Bromodeoxyuridine / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D003106:Colon / Q000166:cytology*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012677:Sensation / Q000187:drug effects*; D016211:Transforming Growth Factor alpha / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D016211:Transforming Growth Factor alpha; D002217:Carbachol; D001973:Bromodeoxyuridine