title: Neural influences on human intestinal epithelium in vitro.
abstract: CONCLUSIONS
  We present the first systematic and, up to now, most comprehensive evaluation of the basic features of epithelial functions, such as basal and nerve-evoked secretion, as well as tissue resistance, in over 2200 surgical specimens of human small and large intestine. We found no evidence for impaired nerve-evoked epithelial secretion or tissue resistance with age or disease pathologies (stomach, pancreas or colon cancer, polyps, diverticulitis, stoma reversal). This indicates the validity of future studies on epithelial secretion or resistance that are based on data from a variety of surgical specimens. ACh mainly mediated nerve-evoked and basal secretion in the small intestine, whereas vasoactive intestinal peptide and nitric oxide were the primary pro-secretory transmitters in the large intestine. The results of the present study revealed novel insights into regional differences in nerve-mediated secretion in the human intestine and comprise the basis by which to more specifically target impaired epithelial functions in the diseased gut.
  Knowledge on basic features of epithelial functions in the human intestine is scarce. We used Ussing chamber techniques to record basal tissue resistance (R-basal) and short circuit currents (ISC; secretion) under basal conditions (ISC-basal) and after electrical field stimulation (ISC-EFS) of nerves in 2221 resectates from 435 patients. ISC-EFS was TTX-sensitive and of comparable magnitude in the small and large intestine. ISC-EFS or R-basal were not influenced by the patients' age, sex or disease pathologies (cancer, polyps, diverticulitis). Ion substitution, bumetanide or adenylate cyclase inhibition studies suggested that ISC-EFS depended on epithelial cAMP-driven chloride and bicarbonate secretion but not on amiloride-sensitive sodium absorption. Although atropine-sensitive cholinergic components prevailed for ISC-EFS of the duodenum, jejunum and ileum, PG97-269-sensitive [vasoactive intestinal peptide (VIP) receptor 1 antagonist] VIPergic together with L-NAME-sensitive nitrergic components dominated the ISC-EFS in colonic preparations. Differences in numbers of cholinergic or VIPergic neurons, sensitivity of epithelial muscarinic or VIP receptors, or stimulus frequency-dependent transmitter release were not responsible for the region-specific transmitter contribution to ISC-EFS. Instead, the low atropine-sensitivity of ISC-EFS in the colon was the result of high cholinesterase activity because neostigmine revealed cholinergic components. Colonic ISC-EFS remained unchanged after tachykinin, P2X, P2Y or A1 and A2 receptor blockade. R-basal was smaller and ISC-basal was higher in the small intestine. TTX and bumetanide decreased ISC-basal in all regions, suggesting nerve-dependent secretory tone. ISC-basal was atropine-sensitive in the small intestine and PG97-269-sensitive in the large intestine. This comprehensive study reveals novel insights into region-specific nerve-mediated secretion in the human small and large intestine.
authors.affiliation: Human Biology, Technische Universität München, Freising, Germany.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Krueger
authors.affiliation: Human Biology, Technische Universität München, Freising, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Michel
authors.affiliation: Surgery, Klinkum Freising, Freising, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Zeller
authors.affiliation: Department of General Surgery, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Ihsan E
authors.initials: IE
authors.lastname: Demir
authors.affiliation: Department of General Surgery, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Güralp O
authors.initials: GO
authors.lastname: Ceyhan
authors.affiliation: Institute of Pathology, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Slotta-Huspenina
authors.affiliation: Human Biology, Technische Universität München, Freising, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Schemann
mesh_terms: D000200:Action Potentials; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001639:Bicarbonates / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D007420:Intestine, Large / Q000166:cytology / Q000294:innervation / Q000378:metabolism; D007421:Intestine, Small / Q000166:cytology / Q000294:innervation / Q000378:metabolism; D017136:Ion Transport; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism* / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D058914:Purinergic Antagonists / Q000494:pharmacology; D026941:Sodium Channel Blockers / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism
chemical_list: D001639:Bicarbonates; D002712:Chlorides; D018727:Muscarinic Antagonists; D026902:Potassium Channel Blockers; D058914:Purinergic Antagonists; D026941:Sodium Channel Blockers; D009569:Nitric Oxide; D014660:Vasoactive Intestinal Peptide