Carbachol induces TGF-alpha expression and colonic epithelial cell proliferation in sensory-desensitised rats
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Signals for the expression of the peptide growth factors epidermal growth factor and transforming growth factor-α (TGFα) in the gastrointestinal mucosa are largely unknown. We have shown earlier that extrinsic afferents in the gastrointestinal tract induce TGFα 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 TGFα expression and epithelial cell proliferation in vivo.
Rats were divided in three groups. Group 1 was treated with vehicle only, group 2 received one single subcutaneous injection of 250 μg/kg of carbachol and animals in group 3 were sensory-desensitised prior to the injection of 250 μg/kg carbachol. TGFα expression and epithelial cell proliferation was evaluated by polymerase chain reaction, Western blot analysis and bromodeoxyuridine staining.
Carbachol induced a significant increase in mucosal epithelial cell proliferation and TGFα expression. Sensory desensitisation did neither abolish the increased TGFα expression nor the increase in epithelial cell proliferation.
Parasympathetic pathways are involved in the control of TGFα expression in gastrointestinal mucosa as well as in epithelial cell proliferation.
KeywordsGastrointestinal nervous system TGFα EGF Experimental model of colitis Carbachol Parasympathetic nerves Extrinsic primary afferents
- 6.Egger B, Procaccino F, Lakshmanan J, Reinshagen M, Hoffmann P, Patel A, Reuben W, Gnanakkan S, Liu L, Barajas L, Eysselein VE (1997) Mice lacking transforming growth factor alpha have an increased susceptibility to dextran sulfate-induced colitis. Gastroenterology 113:825–832CrossRefPubMedGoogle Scholar
- 17.Anderson BK, Karnes WE, Pearson RK (1994) Bile acids regulate the growth rate of transformed colonic epithelium and increase TGF-alpha mRNA levels. Gastroenterology 54:A384Google Scholar
- 18.Hoffmann P, Mazurkiewicz J, Holtmann G, Gerken G, Eysselein VE, Goebell H (2002) Capsaicin-sensitive nerve fibres induce epithelial cell proliferation, inflammatory cell immigration and transforming growth factor-alpha expression in the rat colonic mucosa in vivo. Scand J Gastroenterol 37:414–422CrossRefPubMedGoogle Scholar
- 20.Horikawa Y, Shatos MA, Hodges RR, Zoukhri D, Rios JD, Chang EL, Bernardino CR, Rubin PA, Dartt DA (2003) Activation of mitogen-activated protein kinase by cholinergic agonists and EGF in human compared with rat cultured conjunctival goblet cells. Invest Ophthalmol Vis Sci 44:2535–2544CrossRefPubMedGoogle Scholar
- 25.Liu L, Barajas L (1993) The rat renal nerves during development. Anat Embryol (Berl) 188:345–361Google Scholar
- 36.Taylor P (1990) Cholinergic agonists. In: Goodman Gilman A, Rall TW, Bues AS, Taylor P (eds) The pharmacological basis of therapeutics. Pergamon, New York, pp 122–130Google Scholar
- 37.Kelly SM, Hunter JO (1990) Epidermal growth factor stimulates synthesis and secretion of mucus glycoproteins in human gastric mucosa. Clin Sci (Lond) 79:425–427Google Scholar