Hemin induces active chloride secretion in Caco-2 cells

Aliye Uc, Russell F. Husted, Radhamma L. Giriyappa, Bradley E. Britigan, John B. Stokes

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Abstract

Enterocytes maintain fluid-electrolyte homeostasis by keeping a tight barrier and regulating ion channels. Carbon monoxide (CO), a product of heme degradation, modulates electrolyte transport in kidney and lung epithelium, but its role in regulating intestinal fluid-electrolyte homeostasis has not been studied. The major source of endogenous CO formation comes from the degradation of heme via heme oxygenase. We hypothesized that heme activates electrolyte transport in intestinal epithelial cells. Basolateral hemin treatment increased baseline Caco-2 cell short-circuit currents (Isc) twofold (control = 1.96 ± 0.14 μA/cm2 vs. hemin = 4.07 ± 0.16 μA/cm2, P < 0.01); apical hemin had no effect. Hemin-induced Isc was caused by Cl- secretion because it was inhibited in Cl--free medium, with ouabain, 5-nitro-2-(3-phenylpropylamino) benzole acid (NPPB), or DIDS. Apical electrogenic Na+ channel inhibitor benzamil had no effect on hemin-induced Isc. Hemin did not alter the ability of Caco-2 cells to respond maximally to forskolin, but a soluble guanylate cyclase inhibitor, [1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ) inhibited the effects of hemin. A CO-releasing molecule, tricarbonyldichlororuthenium II, induced active Cl- secretion that was also inhibited with ODQ. We conclude that hemin induces active CP secretion in Caco-2 cells via a cGMP-dependent pathway. These effects are probably the consequence of CO formation. Heme and CO may be important regulators of intestinal fluid-electrolyte homeostasis.

Original languageEnglish (US)
Pages (from-to)G202-G208
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume289
Issue number2 52-2
DOIs
Publication statusPublished - Aug 1 2005

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Keywords

  • Carbon monoxide
  • Cyclic guanosine 5′-monophosphate
  • Electrolyte transport
  • Heme oxygenase
  • Tricarbonyldichlororuthenium II

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

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