Inhibition of enterotoxin-stimulated secretion in CACO-2 cells by 2-chloroadenosine

S. Schulz, W. Zhang, I. Mannan, S. Parkinson, A. Alekseev, A. Terzic, S. A. Waldman

Research output: Contribution to journalArticlepeer-review


Bacteria that produce heat-stable enterotoxin (ST) are a leading cause of secretory diarrhea. ST activates an intestinal-specific guanylyl cyclase (GC-C), leading to the accumulation of intracellular cyclic GMP which results in the opening of the CFTR chloride channel, triggering secretion. Although the signaling cascade mediating ST-induced diarrhea is well characterized, anti-secretory therapy targeting this pathway has not been developed. We examined the ability of 2-chloroadenosine (2ClAdo), an inhibitor of guanylyl cyclase activity, to prevent ST-induced water secretion in Caco-2 intestinal cells. ST induced a chloride current and stimulated net basolateral-to-apical water secretion in these cells, effects that were mimicked by 8-bromocyclic GMP. Pretreatment of cells with 2ClAdo prevented ST-induced chloride current and water secretion, demonstrating that disruption of guanylyl cyclase signaling may be an effective strategy for anti-secretory therapy, and provides the basis for developing mechanism-based treatments for diarrhea caused by enterotoxigenic bacteria.

Original languageEnglish (US)
Pages (from-to)137
Number of pages1
JournalClinical pharmacology and therapeutics
Issue number2
StatePublished - 1999

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)


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