Nitric oxide is a neurotransmitter in the chloride secretory response to serotonin in rat colon.
BACKGROUND
Serotonin (5-hydroxytryptamine [5-HT]) has been shown to induce chloride secretion through a nonadrenergic/noncholinergic neural pathway, mediated by a 5-HT(3) receptor. We hypothesized that 5-HT(3)-induced Cl(-) secretion is ultimately mediated by nitric oxide (NO).


METHODS
Unstripped sheets of rat distal colon were mounted in Ussing chambers and short-circuited. The 5-HT(3) receptor agonist, 2-methyl-5-HT, was added in the absence and presence of the NO synthase inhibitor, L-NAME. Companion studies involved the addition of sodium nitroprusside to tissue that was incubated with or without tetrodotoxin.


RESULTS
L-NAME caused a significant reduction in the 2-methyl-5-HT-induced change in circuit current, in a concentration-dependent manner. Sodium nitroprusside caused a change in circuit current over baseline in 5 minutes. The addition of tetrodotoxin did not significantly alter the change in circuit current; however, the apical Cl(-) channel blocker, anthracene-9-carboxylic acid, abolished this response.


CONCLUSIONS
Neurally mediated Cl(-) secretion in response to 2-methyl-5-HT is inhibited by an NO synthase inhibitor. Exogenous NO mimics this response, which is unaffected by tetrodotoxin. These data suggest that neurally mediated serotoninergic Cl(-) secretion is, in part, mediated by NO. The ability of exogenous NO to induce a change in circuit current in the presence of tetrodotoxin suggests that NO is a final neurotransmitter in this neural-mucosal reflex and therefore acts directly on the enterocyte to induce secretion.
Virginia Commonwealth University, Department of Surgery, Richmond 23298-0519, USA.
M C
MC
Stoner
A M
AM
Scherr
J A
JA
Lee
L G
LG
Wolfe
J M
JM
Kellum
D000818:Animals; D002712:Chlorides / Q000378:metabolism*; D003106:Colon / Q000502:physiology*; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009599:Nitroprusside / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000502:physiology*; D044406:Receptors, Serotonin, 5-HT3; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology
D002712:Chlorides; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D009599:Nitroprusside; D009569:Nitric Oxide; D012701:Serotonin; D013779:Tetrodotoxin; C045918:2-methyl-5-HT; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester