title: Growth hormone regulates intestinal ion transport through a modulation of the constitutive nitric oxide synthase-nitric oxide-cAMP pathway.
abstract: OBJECTIVE
  Growth hormone (GH) directly interacts with the enterocyte stimulating ion absorption and reducing ion secretion induced by agonists of cAMP. Since nitric oxide (NO) is involved in the regulation of transepithelial ion transport and acts as a second messenger for GH hemodynamic effects, we tested the hypothesis that NO may be involved in the resulting effects of GH on intestinal ion transport.
  
  
  METHODS
  Electrical parameters reflecting trans-epithelial ion transport were measured in Caco-2 cell monolayers mounted in Ussing chambers and exposed to GH and cholera toxin (CT) alone or in combination, in the presence or absence of the NO synthase (NOS) inhibitor, Nomega-nitro-L-arginine methyl ester (L-NAME). Similar experiments were conducted to determine cAMP and nitrite/nitrate concentrations. NOS expression was assayed by Western blot analysis.
  
  
  RESULTS
  L-NAME causes total abrogation of absorptive and anti-secretory effects by GH on intestinal ion transport. In addition, L-NAME was able to inhibit the GH-effects on intracellular cAMP concentration under basal conditions and in response to CT. GH induced a Ca(2+)-dependent increase of nitrites/nitrates production, indicating the involvement of the constitutive rather than the inducible NOS isoform, which was directly confirmed by Western blot analysis.
  
  
  CONCLUSIONS
  These results suggest that the GH effects on intestinal ion transport, either under basal conditions or in the presence of cAMP-stimulated ion secretion, are mediated at an intracellular level by the activity of cNOS.
authors.affiliation: Department of Pediatrics, University Federico II, Via S. Pansini, Naples 80131, Italy. berni@unina.it
authors.forename: Roberto
authors.initials: R
authors.lastname: Berni Canani
authors.forename: Pia
authors.initials: P
authors.lastname: Cirillo
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Mallardo
authors.forename: Vittoria
authors.initials: V
authors.lastname: Buccigrossi
authors.forename: Annalisa
authors.initials: A
authors.lastname: Passariello
authors.forename: Serena
authors.initials: S
authors.lastname: Ruotolo
authors.forename: Giulio
authors.initials: G
authors.lastname: De Marco
authors.forename: Francesco
authors.initials: F
authors.lastname: Porcaro
authors.forename: Alfredo
authors.initials: A
authors.lastname: Guarino
mesh_terms: D018938:Caco-2 Cells; D002460:Cell Line; D002772:Cholera Toxin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D013006:Growth Hormone / Q000502:physiology*; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007422:Intestines / Q000166:cytology / Q000187:drug effects; D017136:Ion Transport / Q000187:drug effects* / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D013006:Growth Hormone; D002772:Cholera Toxin; D000242:Cyclic AMP; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester