title: Acute denervation alters the epithelial response to adrenoceptor activation through an increase in alpha1-adrenoceptor expression on villus enterocytes.
abstract: Loss of sympathetic input due to intestinal denervation results in hypersensitivity and increased intestinal secretion. It is unknown whether denervation-induced alterations in intestinal epithelial physiology are the result of changes in adrenoceptors on enterocytes (ENTs). The purpose of this study was to examine adrenoceptor distribution and pharmacology on small intestinal ENTs following acute intestinal denervation. Lewis rats underwent small bowel transplantation (SBT) or sham operation and proximal small intestinal segments were harvested 1, 2 and 4 weeks postoperatively. Intestinal electrolyte movement was assessed using short-circuit current (Isc) measurements of stripped epithelial sheets following stimulation with phenylephrine (PE), an alpha(1)-adrenoceptor agonist. The presence of adrenoceptor subtypes on separated villus and crypt ENTs was assessed using flow cytometry. Alpha(1)-adrenoceptors were found on approximately 27% of jejunal villus ENTs, but not crypt ENTs, following acute extrinsic denervation. ENTs from the Lewis rat have few beta-adrenoceptors. Alpha(1)-adrenoceptor stimulation of acutely denervated intestinal epithelial sheets decreased Isc by -13.45%. This effect was mediated by a reduction in chloride (Cl(-)) secretion; the absence of Cl(-) reversed the Isc to +13.79%. In conclusion, loss of sympathetic innervation to the gastrointestinal epithelium causes acute upregulation of alpha(1)-adrenoceptors on villus ENTs, leading to inhibition of Cl(-) secretion at the villus tip. The increase in adrenoceptors may reflect a compensatory mechanism to combat the increased secretory state of the bowel due to the loss of the sympathetic innervation and tonic control over intestinal secretion.
authors.affiliation: Gastrointestinal Research Group, University of Calgary, 3330 Hospital Drive, Calgary, Alberta, Canada T2N 4N1.
authors.forename: Carolyn J
authors.initials: CJ
authors.lastname: Baglole
authors.forename: David L
authors.initials: DL
authors.lastname: Sigalet
authors.forename: Gary R
authors.initials: GR
authors.lastname: Martin
authors.forename: Shengtao
authors.initials: S
authors.lastname: Yao
authors.forename: Jon B
authors.initials: JB
authors.lastname: Meddings
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003714:Denervation; D020895:Enterocytes / Q000201:enzymology / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000201:enzymology / Q000378:metabolism*; D007421:Intestine, Small / Q000166:cytology / Q000201:enzymology / Q000294:innervation*; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D018340:Receptors, Adrenergic, alpha-1 / Q000096:biosynthesis / Q000235:genetics*; D013393:Sucrase / Q000502:physiology
chemical_list: D018340:Receptors, Adrenergic, alpha-1; D013393:Sucrase