Peptide YY inhibition of rat gastric enterochromaffin-like cell function.
OBJECTIVE
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.
Zeng
N
N
CURE/Digestive Diseases Research Center, VA/UCLA, USA.
Walsh
J H
JH
Kang
T
T
Wu
S V
SV
Sachs
G
G
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D005755:Gastrins / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D005768:Gastrointestinal Hormones / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects*; D019894:Peptide YY; D010455:Peptides / Q000494:pharmacology*; D037342:Pertussis Toxin; D051381:Rats; D011964:Receptors, Gastrointestinal Hormone / Q000187:drug effects; D013004:Somatostatin / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D005755:Gastrins; D005768:Gastrointestinal Hormones; D010455:Peptides; D011964:Receptors, Gastrointestinal Hormone; D010566:Virulence Factors, Bordetella; C082172:peptide YY receptor; D019894:Peptide YY; D013004:Somatostatin; D037342:Pertussis Toxin; D002118:Calcium