The role of serotonin in the canine secretory response to cholera toxin in vivo
LaRosa, C.A.; Sherlock, D.; Kimura, K.; Pimpl, W.; Money, S.R.; Jaffe, B.M.
Journal of Pharmacology and Experimental Therapeutics 251(1): 71-76
1989
ISSN/ISBN: 0022-3565 PMID: 2795472 Document Number: 345719
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 .mu.g of cholera toxin induced secretion; fluxes of water (basal, 32.3 .+-. 11.1; 6 hr, -541 .+-. 35 .mu.l/min), sodium (basal, 9.0 .+-. 2.8; 6 hr, -78.3 .+-. 5.6 .mu.Eq/min), chloride (basal, 3.8 .+-. 1.5; 6 hr, -65.7 .+-. 4.0 .mu.Eq/min) and potassium (basal, 0.10 .+-. 0.08; 6 hr, -2.80 .+-. 0.18 .mu.Eq/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 .mu.g/kg/min) during the 4th hr in four dogs exposed to cholera toxin. The lower dose of toxin (5 .mu.g) 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 .mu.g/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. Finally, i.v. verapamil and ketanserin were shown, in five dogs with jejunal Thirty-Vella loops, to convert intestinal fluxes of water and electrolytes induced by endoluminal serotonin perfusion (600 ng/min) from secretion to absorption. Thus, our data suggest that although the toxin liberates serotonin into the small intestinal lumen, this amine is unlikely to mediate the secretory effects of cholera toxin.