REGULATION OF PEPTIDE YY HOMEOSTASIS BY GASTRIC-ACID AND GASTRIN

Peptide YY (PYY) is a gut hormone localized primarily in the distal bo wel. Because circulating PW inhibits gastric acid secretion, we invest igated the effects of gastric acid secretion and gastrin on gene expre ssion and secretion of PW. In conscious dogs, PYY release in response to oral food was inhibited (P < 0.05) by pharmacologic inhibition of g astric acid secretion (omeprazole, famotidine). In rats, omeprazole tr eatment resulted in a significant elevation in serum gastrin concentra tions and a simultaneous decrease in PYY messenger RNA (mRNA) and pept ide levels in the colon; administration of a gastrin receptor antagoni st (L365, 260) prevented the inhibitory actions of omeprazole on colon ic PYY mRNA levels. In athymic-nude mice, implantation of a human gast rinoma resulted in an elevation of serum gastrin concentrations and a concomitant depression of colonic PYY mRNA levels. We conclude that en dogenous gastric acid secretion up-regulates PYY release and PYY mRNA expression. Circulating gastrin acts to down-regulate PYY release and PYY mRNA expression. This study provides evidence that foregut functio ns (i.e., gastric acid secretion and gastrin release) exert control ov er an antiacid signal (e.g. PYY release) emanating from the hindgut.