title: Muscarinic cholinergic and alpha 2-adrenergic receptors in the epithelium and muscularis of the human ileum.
abstract: The aim of this study was to characterize the binding and functional properties of muscarinic cholinergic (MCh) and alpha 2-adrenergic receptors in the human ileum to provide insight into pharmacologic strategies for managing urinary and fecal incontinence after bladder and rectal replacement with intestinal segments. MCh and alpha 2-adrenergic binding sites were characterized in the epithelium and muscularis of eight human ileal segments with 3H-N-methylscopolamine and 3H-rauwolscine, respectively. The dissociation constant for 3H-N-methylscopolamine in the epithelium and muscularis was 0.32 +/- 0.07 nmol/L and 0.45 +/- 0.10 nmol/L, respectively (p = 0.32). The MCh receptor content was approximately eightfold greater in the muscularis compared with the epithelium (p = 0.008). The dissociation constant for 3H-rauwolscine in the muscularis and epithelium was 2.55 +/- 0.42 nmol/L and 2.03 +/- 0.19 nmol/L, respectively (p = 0.29). The alpha 2-adrenoceptor density was twofold greater in the epithelium compared with the muscularis (p = 0.05). Noncumulative concentration-response experiments were performed with carbachol, an MCh agonist, and UK-14304, a selective alpha 2-adrenergic agonist. The epithelium did not contract in the presence of high concentrations of carbachol and UK-14304. The muscularis preparations were responsive only to carbachol. The muscularis contains primarily MCh receptors mediating smooth muscle contraction. The alpha 2-adrenoceptors are localized primarily to the epithelium and may regulate water secretion in the intestine. The distribution and functional properties of ileal MCh and alpha 2-adrenergic receptors provide a theoretic basis for the treatment of incontinence after bladder and rectal replacement with intestinal segments.
authors.affiliation: Division of Urologic Surgery, Jewish Hospital of St. Louis, Washington University Medical Center, Mo.
authors.forename: H
authors.initials: H
authors.lastname: Lepor
authors.forename: G
authors.initials: G
authors.lastname: Rigaud
authors.forename: E
authors.initials: E
authors.lastname: Shapiro
authors.forename: M
authors.initials: M
authors.lastname: Baumann
authors.forename: I J
authors.initials: IJ
authors.lastname: Kodner
authors.forename: J W
authors.initials: JW
authors.lastname: Fleshman
mesh_terms: D004848:Epithelium / Q000378:metabolism; D006801:Humans; D007082:Ileum / Q000378:metabolism*; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000378:metabolism*; D019832:N-Methylscopolamine; D010276:Parasympatholytics / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000378:metabolism*; D012602:Scopolamine Derivatives / Q000378:metabolism; D014316:Tritium; D015016:Yohimbine / Q000378:metabolism
chemical_list: D010276:Parasympatholytics; D011942:Receptors, Adrenergic, alpha; D011976:Receptors, Muscarinic; D012602:Scopolamine Derivatives; D014316:Tritium; D015016:Yohimbine; D011189:Potassium Chloride; D019832:N-Methylscopolamine