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.
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D002927:Cimetidine / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D007082:Ileum / Q000502:physiology*; D007408:Intestinal Absorption / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011817:Rabbits; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D014655:Vascular Resistance / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D002927:Cimetidine; D003000:Clonidine; D009638:Norepinephrine