Peptide YY inhibition of prostaglandin-induced intestinal secretion is haloperidol-sensitive in humans.

Background & Aims: It is uncertain whether peptide YY (PYY) inhibits human intestinal secretion directly through enterocyte receptors or via indirect neural mechanisms. Thus, the effect of PYY on prostaglandin E2 (PGE2)-induced jejunal secretion in normal volunteers was measured, and it was determined whether a dopamine and sigma antagonist affected PYY effect.

Methods: Jejunal absorption of water and electrolytes was measured by a perfusion method in 6 volunteers. A double-blind crossover study was performed, involving intraluminal infusion of PGE2, intravenous infusion of human PYY, and intramuscular injection of haloperidol or placebo.

Results: PGE2 induced net secretion of water and electrolytes (P < 0.01 vs. basal). The effect of PGE2 was reduced by about half with 30 pmol x kg(-1) x h(-1) of PYY (plasma PYY, 96 +/- 12 pg/mL) and suppressed by 90 pmol x kg(-1) x h(-1) of PYY (P < 0.01; plasma PYY, 268 +/- 22 pg/mL). Plasma PYY was correlated negatively (P < 0.01) with net fluxes of water, Cl-, Na+, and K+. Haloperidol suppressed the effect of PYY on PGE2-induced secretion (P < 0.05).

Conclusions: PYY administered in doses producing slightly supraphysiological plasma levels inhibits PGE2-induced secretion in normal humans. Sigma or dopamine receptors (probably neuronal ones) are involved in this effect.