Effect of cyclooxygenase inhibition on serotonin-induced chloride secretion from rat distal colon.
BACKGROUND
Serotonin is a well-known mediator of intestinal chloride secretion. The effects of exogenous 5-hydroxytryptamine (5-HT) can be demonstrated experimentally by a rise in short-circuit current, which is proportional to active electrogenic chloride secretion. Prostaglandin E2 is also an intestinal secretagogue and has been implicated in certain diarrheal illnesses. The aim of this study was to evaluate the effect of a cyclooxygenase inhibitor on 5-HT-stimulated ion transport.


METHODS
Full- or partial-thickness sheets of rat colon were mounted in Ussing chambers and placed under short-circuit conditions. 5-HT or the specific 5-HT3 receptor agonist, 2-methyl-5-HT, was added in the absence and presence of the cyclooxygenase inhibitor, piroxicam.


RESULTS
The overall drug effect was statistically significant at two concentrations (10(-5) and 5 x 10(-4) mol) of piroxicam when compared with 5-HT alone (P < or = .005; ANOVA, n = 8). The inhibitory effect of piroxicam (10(-5)) was statistically significant when compared to 2-methyl-5-HT alone (P < .01; ANOVA, n = 5). Piroxicam did not significantly affect baseline current.


CONCLUSIONS
Exogenous 5-HT applied to an in vitro preparation of rat distal colon induces chloride secretion that is significantly inhibited by the cyclooxygenase inhibitor, piroxicam. It appears that the cyclooxygenase pathway plays a major role in the mediation of the secretory response to exogenous serotonin in vitro.
Departments of Surgery and Pathology, Virginia Commonwealth University Medical Center, Richmond, VA 23298-0519, USA.
Brian N
BN
King
Sheikh M
SM
Haque
Zach M
ZM
Ellis
Luke G
LG
Wolfe
John M
JM
Kellum
D000818:Animals; D002712:Chlorides / Q000378:metabolism*; D003106:Colon / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D044406:Receptors, Serotonin, 5-HT3 / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology*
D002712:Chlorides; D016861:Cyclooxygenase Inhibitors; D044406:Receptors, Serotonin, 5-HT3; D012701:Serotonin; D015232:Dinoprostone