Peptide YY inhibition of prostaglandin-induced intestinal secretion is haloperidol-sensitive in humans.
OBJECTIVE
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.
Rozé
C
C
INSERM Unité 410, Faculté X Bichat, Paris, France.
Molis
C
C
Xiaomei
F C
FC
Ropert
A
A
Genève
J
J
Galmiche
J P
JP
D018592:Cross-Over Studies; D015232:Dinoprostone / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004311:Double-Blind Method; D004435:Eating; D004573:Electrolytes / Q000378:metabolism; D006220:Haloperidol / Q000494:pharmacology*; D006801:Humans; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D007583:Jejunum / Q000187:drug effects* / Q000378:metabolism*; D019894:Peptide YY; D010455:Peptides / Q000097:blood / Q000494:pharmacology*; D014867:Water / Q000378:metabolism
D018492:Dopamine Antagonists; D004573:Electrolytes; D010455:Peptides; D014867:Water; D019894:Peptide YY; D006220:Haloperidol; D015232:Dinoprostone