LUMINAL ADRENERGIC AGENTS MODULATE ILEAL TRANSPORT - DISCRIMINATION BETWEEN ALPHA-1 AND ALPHA-1 RECEPTORS

Luminal alpha-adrenergic agonists alter deal water, ion, and glucose t ransport by a local mechanism. This study tested the hypothesis that l uminal adrenergic agents modulate deal transport selectively, via spec ific alpha(1) and alpha(2) receptors. Absorption studies (n = 72) were performed on dogs with 25-cm ileal Thiry-Vella fistulas (TVF). Perfus ion with (C-14) polyethylene glycol was used to calculate absorption o f water, ions, and glucose from the TVF. Experiments included four 1-h our periods. Agonists used were phenylephrine (alpha(1)), clonidine (a lpha(2)), and norepinephrine (alpha(1) > alpha(2) and beta). Antagonis ts used were terazosin (alpha 1) and yohimbine (alpha(2)). Phenylephri ne and norepinephrine caused significant increases in water and ion ab sorption (p<0.05). Clonidine caused significant decreases in water, io n, and glucose absorption (p<0.05). Terazosin and yohimbine had no eff ect alone. Terazosin prevented the proabsorptive effect of phenylephri ne and norepinephrine, and yohimbine blocked the prosecretory effect o f clonidine. Yohimbine significantly increased the norepinephrine-indu ced proabsorptive effect. Luminal alpha-adrenergic agents selectively modulate deal transport. Alpha(1)-receptor activation causes a proabso rptive response, whereas alpha(2)-receptor activation causes a prosecr etory response. The combination of a luminally administered mixed alph a- beta-adrenergic agonist (norepinephrine) with alpha(2) receptor blo ckade (yohimbine) may prove useful in pathologic secretory states such as intestinal transplants, diabetic diarrhea, or diarrhea-associated endocrinopathies.