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Vol. 279, Issue 3, G575-G581, September 2000

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

Hong Yang, Keishi Kawakubo, Helen Wong, Gordon Ohning, John Walsh, and Yvette Taché

CURE: Digestive Diseases Research Center, Veterans Affairs Greater Los Angeles Healthcare System, and Digestive Diseases Division, Department of Medicine and Brain Research Institute, School of Medicine, University of California, Los Angeles, California 90073

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 µmol/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 · kg¹ · h¹ 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 · kg¹ · h¹). When injected intracisternally, the PYY antibody (280 µg/rat) reversed intracisternal PYY (2.4 pmol)- and intravenous PYY (1 nmol · kg¹ · h¹)-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.

immunoneutralization; vagus; dorsal vagal complex

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Deceased 14 June 2000.

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