LUMINAL DOPAMINE MODULATES CANINE ILEAL WATER AND ELECTROLYTE TRANSPORT

Previous studies have suggested that dopamine stimulates active ileal ion absorption via alpha(2)-adrenergic or dopaminergic receptor activation. Identification of a dopamine 1a receptor on rat enterocytes located in intestinal crypts prompted this investigation of the effect of luminally administered dopamine on water and ion transport in the canine ileum. Absorption studies (n = 27) were performed in dogs with 25-cm ileal Thiry-Vella fistulas. Perfusion with [C-14 pEG was used to calculate absorption of water and electrolytes from the Thiry-Vella fistula, Experiments consisted of three l-hr periods: basal, luminal drug infusion at 10(-4) M, and recovery. Agonists used included dopamine (DOP: alpha-adrenergic, D-1 and D-2 receptor) and SKF 38393 (D-1 receptor). Antagonists used included terazosin (TZ: alpha(1)) and yohimbine (YOH: alpha(2)). DOP caused significant increases in water and electrolyte absorption. TZ and YOH prevented the dopamine-induced proabsorptive response. Luminal DOP may serve as a proabsorptive modulator of ileal transport, acting via alpha(1), alpha(2), and dopaminergic receptors. The development of more potent proabsorptive dopamine analogs, which maintain the ability to broadly activate mucosal receptors, may be useful in such clinical situations as diabetic diarrhea, short gut syndrome, or following small bowel transplantation.