PEPTIDE YY INHIBITION OF RAT GASTRIC ENTEROCHROMAFFIN-LIKE CELL-FUNCTION

Background & Aims: The cellular target for peptide YY (PW) inhibition of gastric acid secretion is unknown, The aim of this study was to det ermine whether PW inhibits histamine release from isolated enterochrom affin-like (ECL) cells by stimulation of a selective Y receptor, Metho ds: Isolated rat gastric ECL cells were analyzed in short-term culture for histamine release and for changes in intracellular calcium concen tration using video imaging, Results: Gastrin-stimulated histamine rel ease was inhibited with a 50% inhibiting concentration of 2.10(-9) mol /L, Inhibition of histamine release and of calcium entry by PW and [Pr o(34)]PYY and no effect of PW(3-36) characterizes an inhibitory Y-1 re ceptor subtype. Reverse-transcription polymerase chain reaction of ECL cell RNA showed that the receptor was the nontruncated Y-1 isoform, T he inhibitory action of PYY and related peptides on gastrin-stimulated histamine release and calcium signaling was eliminated by pretreatmen t with 200 ng/mL pertussis toxin. Additive but not synergistic inhibit ory effects of PYY and somatostatin on gastrin-stimulated histamine re lease were observed, Conclusions: Activation of a Y-1 inhibitory recep tor subtype present on the gastric ECL cell that inhibits gastrin-indu ced ECL cell histamine release and Ca2+ entry by activation of a G(i) or G(o) class of protein may account for inhibition of gastric acid se cretion by PYY released from the small intestine.