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.
Barry
M K
MK
Department of Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland.
Aloisi
J D
JD
Pickering
S P
SP
Yeo
C J
CJ
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D004285:Dogs; D005260:Female; D007082:Ileum / Q000378:metabolism* / Q000601:surgery; D007408:Intestinal Absorption / Q000187:drug effects* / Q000502:physiology; D007412:Intestinal Fistula; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects* / Q000502:physiology; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects* / Q000502:physiology; D014882:Water-Electrolyte Balance / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000318:Adrenergic beta-Agonists; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2