Luminal adrenergic agents modulate ileal transport: discrimination between alpha 1 and alpha 2 receptors

Luminal alpha-adrenergic agonists alter ileal water, ion, and glucose transport by a local mechanism. This study tested the hypothesis that luminal adrenergic agents modulate ileal transport selectively, via specific alpha 1 and alpha 2 receptors. Absorption studies (n = 72) were performed on dogs with 25-cm ileal Thiry-Vella fistulas (TVF). Perfusion with (14C) polyethylene glycol was used to calculate absorption of water, ions, and glucose from the TVF. Experiments included four 1-hour periods. Agonists used were phenylephrine (alpha 1), clonidine (alpha 2), and norepinephrine (alpha 1 > alpha 2 and beta). Antagonists used were terazosin (alpha 1) and yohimbine (alpha 2). Phenylephrine and norepinephrine caused significant increases in water and ion absorption (p < 0.05). Clonidine caused significant decreases in water, ion, and glucose absorption (p < 0.05). Terazosin and yohimbine had no effect alone. Terazosin prevented the proabsorptive effect of phenylephrine and norepinephrine, and yohimbine blocked the prosecretory effect of clonidine. Yohimbine significantly increased the norepinephrine-induced proabsorptive effect. Luminal alpha-adrenergic agents selectively modulate ileal transport. Alpha 1-receptor activation causes a proabsorptive response, whereas alpha 2-receptor activation causes a prosecretory response. The combination of a luminally administered mixed alpha- and beta-adrenergic agonist (norepinephrine) with alpha 2 receptor blockade (yohimbine) may prove useful in pathologic secretory states such as intestinal transplants, diabetic diarrhea, or diarrhea-associated endocrinopathies.