title: Both serotonin and a nitric-oxide donor cause chloride secretion in rat colonocytes by stimulating cGMP.
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.
authors.affiliation: Virginia Commonwealth University, Department of Surgery, Richmond, VA, USA.
authors.forename: M C
authors.initials: MC
authors.lastname: Stoner
authors.forename: J M
authors.initials: JM
authors.lastname: Kellum
mesh_terms: D000818:Animals; D002712:Chlorides / Q000378:metabolism*; D003106:Colon / Q000166:cytology / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D010069:Oxadiazoles / Q000494:pharmacology; D010078:Oxazines / Q000494:pharmacology; D011073:Polyamines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology*
chemical_list: D002712:Chlorides; D004791:Enzyme Inhibitors; C111257:NS 2028; D020030:Nitric Oxide Donors; D010069:Oxadiazoles; D010078:Oxazines; D011073:Polyamines; C005391:diethylenetriamine; D012701:Serotonin; C045918:2-methyl-5-HT; D006162:Guanylate Cyclase; D006152:Cyclic GMP