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.
Yang
H
H
CURE: Digestive Diseases Research Center, Veterans Affairs Greater Los Angeles Healthcare System, Department of Medicine and Brain Research Institute, School of Medicine, University of California, 90073, USA. hoyang@ucla.edu
Kawakubo
K
K
Wong
H
H
Ohning
G
G
Walsh
J
J
Taché
Y
Y
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001923:Brain Chemistry / Q000502:physiology*; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000294:innervation* / Q000378:metabolism; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D009500:Neutralization Tests; D010446:Peptide Fragments; D019894:Peptide YY / Q000276:immunology / Q000494:pharmacology*; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D051381:Rats; D017207:Rats, Sprague-Dawley; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D014630:Vagus Nerve / Q000502:physiology
D000906:Antibodies; D010446:Peptide Fragments; D019894:Peptide YY; C061785:peptide YY (3-36); D013973:Thyrotropin-Releasing Hormone; C027979:L-pyroglutamyl-L-histidyl-3,3-dimethylprolinamide; D011761:Pyrrolidonecarboxylic Acid