Peripheral PYY inhibits intracisternal TRH-induced gastric acid secretion by acting in the brain.

The site of action of peripheral peptide YY (PYY)-induced inhibition of vagally stimulated gastric acid secretion was studied using immunoneutralization with PYY antibody in urethan-anesthetized rats. Gastric acid secretion (59+/-7 micromol/90 min) stimulated by intracisternal injection of the stable thyrotropin-releasing hormone (TRH) analog RX-77368 (14 pmol/rat) was dose-dependently inhibited by 52%, 69%, and 83% by intravenous infusion of 0.25, 0.5, and 1.0 nmol. kg(-1) x h(-1) PYY, respectively. PYY or PYY(3-36) (2.4 pmol/rat) injected intracisternally also inhibited the acid response to intracisternal RX-77368 by 73% and 80%, respectively. Intravenous pretreatment with PYY antibody (4.5 mg/rat), which shows a 35% cross-reaction with PYY(3-36) by RIA, completely prevented the inhibitory effect of intravenously infused PYY (1 nmol x kg(-1) x h(-1)). When injected intracisternally, the PYY antibody (280 microg/rat) reversed intracisternal PYY (2.4 pmol)- and intravenous PYY (1 nmol x kg(-1) x h(-1))-induced inhibition of acid response to intracisternal RX-77368 by 64% and 93.5%, respectively. These results provide supporting evidence that peripheral PYY inhibits central vagal stimulation of gastric acid secretion through an action in the brain.