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Surgery. 2001 Aug;130(2):236-41.

Both serotonin and a nitric-oxide donor cause chloride secretion in rat colonocytes by stimulating cGMP.

Author information

1
Virginia Commonwealth University, Department of Surgery, Richmond, VA, USA.

Abstract

BACKGROUND:

Previous studies have demonstrated that an antagonist of nitric oxide synthase inhibits neurally mediated chloride secretion in response to serotonin (5-HT). The purpose of this study was to demonstrate that chloride secretion in rat colonocytes that were caused by stimulation of neural 5-HT receptors is mediated by way of a nitrergic pathway that involves the activation of guanylate cyclase.

METHODS:

The nitric oxide (NO) donor, diethylenetriamine/NO (DNO), was added to an enriched suspension of rat colonocytes that were preloaded with (36)Cl(-). In parallel experiments, DNO (1 micromol/L) was added to cells that were pretreated with the specific inhibitor of soluble guanylate cyclase, NS2028 (2 micromol/L). In additional studies, the neural 5-HT(3) receptor agonist, 2-methyl-5-HT (10 micromol/L), was added to the serosal surface of muscle-stripped sheets of rat colonic mucosa that were mounted in Ussing chambers under voltage clamp conditions, both in the absence and presence of NS2028 (20 mircro).

RESULTS:

DNO induced 18.0% +/- 8.0% greater (36)Cl(-) efflux than controls (P <.05; n = 14 animals). This efflux was abolished by previous treatment with NS2028. In the chamber experiments, 2-methyl-5-HT induced electrogenic chloride secretion that was significantly inhibited by previous treatment with NS2028 (2.2 +/- 0.5 microA/cm(2) vs 13.1 +/- 2.1 microA/cm(2); P <.001; n = 9 animals).

CONCLUSIONS:

The predominant secretomotor neurotransmitter that mediates the chloride secretory effects of 5-HT in vitro is nitric oxide. Both the secretory effect initiated at the 5-HT(3) receptor on enteric neurons and at the NO(-) receptor on the rat colonocytes are mediated through the activation of intracellular guanylate cyclase and the production of cyclic guanosine monophosphate.

PMID:
11490355
DOI:
10.1067/msy.2001.115903
[Indexed for MEDLINE]

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