Discrimination between alpha 1- and alpha 2-adrenergic receptors in the isolated perfused ileum

Adrenergic control over intestinal homeostasis has been associated with changes in intestinal vascular resistance, motility, and transport. With the use of selective alpha-adrenergic agents, this study was designed to discriminate between the vascular and transport effects. Rabbit 20 cm ileal segments (n = 31) were vascularly perfused at a rate of 1.5 ml/min by means of a modified Krebs solution containing 15% to 20% red cells. The intestinal lumen was perfused with an isotonic solution containing carbon 14-polyethylene glycol as a nonabsorbable marker. Net fluxes of water and electrolytes were calculated during 20-minute basal, experimental, and recovery periods. Norepinephrine (mixed alpha 1- and alpha 2-agonist) significantly increased intestinal absorption and vascular resistance. Phenylephrine (alpha 1-agonist) significantly increased vascular resistance without altering transport. Clonidine (alpha 2-agonist) stimulated intestinal absorption without changing vascular perfusion pressure. Yohimbine (alpha 2-antagonist) prevented norepinephrine-induced absorption but had no effect on norepinephrine-induced increases in perfusion pressure. In this isolated perfused whole gut model, alpha 1-adrenergic stimulation was responsible for increases in vascular resistance, and alpha 2-adrenergic stimulation was responsible for increases in the absorption of water and electrolytes. The ability to discriminate between alpha 1- and alpha 2-effects has potential therapeutic implications in patients with malabsorption and diarrhea.