Verapamil Reversal of Serotonin-Induced Jejunal Secretion of Water and Electrolytes in Awake Dogs

Intestinal handling of water and electrolytes was monitored in 5 conscious dogs with chronic 25-cm Thiry--Vella loops of proximal jejunum using a neutral isosmotic perf usate containing [¹⁴C]polyethyl-ene glycol as a recovery marker. Under basal conditions the animals absorbed water, Na⁺, and Cl^-, and there was minimal nonsignificant secretion of K⁺. Intravenous serotonin infusion (30 μg/kg.min) increased circulating hormone levels to 937 ± 131 ng/ml and induced significant secretion of water (-150 ± 52 μ/min), Na⁺ (-22.8 ± 8.4 μEq/min), Cl^-(-23.5 ± 6.0 μEg/min), and K⁺ (-1.79 ± 0.34 μEg/min). Simultaneous infusion of verapamil, a calcium channel blocker, at 8.3 μg/kg min, reversed the intestinal secretion to absorption of all these parameters (144 ± 32 μl/min, 15.1 ± 5.1 μEg/min, 10.3 ± 3.0 μEq/min, and 0.12 ± 0.23 μEg/min, respectively). This was accompanied by a significant improvement in the clinical appearance of the animals, decreased visible agitation, and cessation of defecation. Cessation of verapamil infusion (leaving the serotonin infusion unopposed) resulted in prompt return to the secretory state. Serum electrolytes did not change significantly, with the exception of potassium, which fell from 5.1 ± 0.2 to 4.1 ± 0.1 mg/dl. In control experiments (no serotonin), verapamil had an insignificant stimulatory effect on the absorption of water, Na⁺, and Cl^-whereas the effect on K⁺ was significant (-0.2 ± 0.2 to +0.4 ± 0.1 μEq/min; p < 0.05). These data support the role of calcium in modulating the effects of serotonin, and they suggest a new promising technology for the management of serotonininduced intestinal secretion such as that seen in the carcinoid syndrome.