Peptide YY inhibition of rat gastric enterochromaffin-like cell function.

BACKGROUND & AIMS: The cellular target for peptide YY (PYY) inhibition of gastric acid secretion is unknown. The aim of this study was to determine whether PYY inhibits histamine release from isolated enterochromaffin-like (ECL) cells by stimulation of a selective Y receptor.

METHODS

Isolated rat gastric ECL cells were analyzed in short-term culture for histamine release and for changes in intracellular calcium concentration using video imaging.

RESULTS

Gastrin-stimulated histamine release was inhibited with a 50% inhibiting concentration of 2.10(-9) mol/L. Inhibition of histamine release and of calcium entry by PYY and [Pro34]PYY and no effect of PYY(3-36) characterizes an inhibitory Y1 receptor subtype. Reverse-transcription polymerase chain reaction of ECL cell RNA showed that the receptor was the nontruncated Y1 isoform. The inhibitory action of PYY and related peptides on gastrin-stimulated histamine release and calcium signaling was eliminated by pretreatment with 200 ng/mL pertussis toxin. Additive but not synergistic inhibitory effects of PYY and somatostatin on gastrin-stimulated histamine release were observed.

CONCLUSIONS

Activation of a Y1 inhibitory receptor subtype present on the gastric ECL cell that inhibits gastrin-induced ECL cell histamine release and Ca2+ entry by activation of a Gi or G(o) class of protein may account for inhibition of gastric acid secretion by PYY released from the small intestine.