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 vag ally stimulated gastric acid secretion was studied using immunoneutralizati on with PYY antibody in urethan-anesthetized rats. Gastric acid secretion ( 59 +/- 7 mmol/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).h(-1) PYY, respectively. PYY or PYY3-36 (2.4 pmol /rat) injected intracisternally also inhibited the acid response to intraci sternal RX-77368 by 73% and 80%, respectively. Intravenous pretreatment wit h PYY antibody (4.5 mg/rat), which shows a 35% cross-reaction with PYY3-36 by RIA, completely prevented the inhibitory effect of intravenously infused PYY (1 nmol.kg(-1).h(-1)). When injected intracisternally, the PYY antibod y (280 mu g/rat) reversed intracisternal PYY (2.4 pmol)- and intravenous PY Y (1 nmol.kg(-1).h(-1))-induced inhibition of acid response to intracistern al RX-77368 by 64% and 93.5%, respectively. These results provide supportin g evidence that peripheral PYY inhibits central vagal stimulation of gastri c acid secretion through an action in the brain.