PT  - JOURNAL ARTICLE
AU  - C A LaRosa
AU  - D Sherlock
AU  - K Kimura
AU  - W Pimpl
AU  - S R Money
AU  - B M Jaffe
TI  - The role of serotonin in the canine secretory response to cholera toxin in vivo.
DP  - 1989 Oct 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 71--76
VI  - 251
IP  - 1
4099  - http://jpet.aspetjournals.org/content/251/1/71.short
4100  - http://jpet.aspetjournals.org/content/251/1/71.full
SO  - J Pharmacol Exp Ther1989 Oct 01; 251
AB  - This study was initiated to evaluate the role of serotonin in cholera toxin-induced jejunal secretion of water and electrolytes. Chronic Thiry-Vella loops, constructed in six dogs, were perfused with an isosmotic neutral perfusate containing [14C]polyethylene glycol as the recovery marker. Fluxes of water, sodium, chloride and potassium were calculated and immunoreactive serotonin levels were measured in blood and effluent perfusates. Intraluminal application of 20 micrograms of cholera toxin induced secretion; fluxes of water (basal, 32.3 +/- 11.1; 6 hr, -541 +/- 35 microliter/min), sodium (basal, 9.0 +/- 2.8; 6 hr, -78.3 +/- 5.6 microEq/min), chloride (basal, 3.8 +/- 1.5; 6 hr, -65.7 +/- 4.0 muEq/min) and potassium (basal, 0.10 +/- 0.08; 6 hr, -2.80 +/- 0.18 muEq/min) were all significantly different from basal. Serum electrolytes remained normal, except that potassium fell from 4.9 +/- 0.5 to 3.9 +/- 0.2 mEq/l. Although circulating serotonin levels did not change from base line (180.9 +/- 29.3 ng/ml), effluent concentrations increased significantly from 68.2 +/- 4.6 to 81.1 +/- 5.0 ng/ml (at 3 hr) and jejunal outputs increased from 136.6 +/- 10.2 to 205.1 +/- 10.1 ng/min (at 6 hr). In a separate set of experiments, verapamil was infused i.v. (12.5 micrograms/kg/min) during the 4th hr in four dogs exposed to cholera toxin. The lower dose of toxin (5 micrograms) induced secretion which was unaffected by the calcium channel blocker. In another series of studies, ketanserin (a 5-HT2 receptor blocker) was infused i.v. at 33 micrograms/kg/min during the 4th hr in four additional dogs exposed to the lower dose of cholera toxin. This potent serotonin antagonist failed to inhibit cholera toxin-induced jejunal secretion.(ABSTRACT TRUNCATED AT 250 WORDS)