Luminal Adrenergic Agonists Modulate Ileal Transport by a Local Mechanism

Abstract

Intestinal transport is controlled by neural pathways, hormones, and luminal agents. Luminal adrenergic agents influence water and ion transport in the jejunum. This study tested two hypotheses: (i) luminal adrenergic agents influence ileal water, ion and glucose transport, and (ii) luminal adrenergic agents exert their effects locally and selectively. Absorption studies (n = 46) were performed on dogs with two adjacent 25-cm ileal Thiry-Vella fistulas (TVF). Perfusion with [14C]polyethylene glycol was used to calculate absorption of water, ions, and glucose from the distal TVF. Experiments were composed of three 1-hr periods: basal, luminal adrenergic agonist infusion, and recovery. In group 1 the adrenergic agonists were administered to the distal TVF: norepinephrine (α1 > α2 and β), phenylephrine (α1), clonidine (α2), and isoproterenol (β). In group 2 the adrenergic agonists were administered to the proximal TVF, with absorption measured in the distal TVF. In group 1 norepinephrine and phenylephrine caused a significant increase in water absorption (P < 0.05). Clonidine and isoproterenol caused decreased absorption of water and ions, with clonidine causing significantly decreased absorption (P < 0.05) of water, ions, and glucose. In group 2 there were no changes in distal TVF absorption. Luminal adrenergic agents did not alter the heart rate in either group. Luminal adrenergic agonists modulate ileal transport via a local mechanism. A proabsorptive response is observed with α1 agonists, while α2 and β agonists cause a prosecretory effect. Inhibition of glucose absorption appears to be selectively mediated via the α2-adrenergic receptor. Luminal proabsorptive α1-adrenergic agents may prove useful in pathologic secretory states such as intestinal transplants, diabetic diarrhea, or diarrhea-associated endocrinopathies.