Expression cloning and characterization of the canine parietal cell gastrin receptor

A. S. Kopin, Y. M. Lee, E. W. McBride, L. J. Miller, M. Lu, H. Y. Lin, L. F. Kolakowski, M. Beinborn

Research output: Contribution to journalArticle

450 Scopus citations

Abstract

Gastrin is an important stimulant of acid secretion by gastric parietal cells and is structurally related to the peptide hormone cholecystokinin (CCK). The pharmacologic properties of the parietal cell gastrin receptor are very similar to the predominant CCK receptor in the brain, CCK-B. Neither the gastrin nor the CCK-B receptor have been cloned thus far, making it difficult to resolve whether these two receptors are distinct. We have isolated a clone encoding the canine gastrin receptor by screening a parietal cell cDNA expression library using a radioligand-binding strategy. Nucleotide sequence analysis revealed an open reading frame encoding a 453-amino acid protein with seven putative hydrophobic transmembrane domains and significant homology with members of the β-adrenergic family of G protein-coupled receptors. The expressed recombinant receptor shows the same binding specificity for gastrin/CCK agonists and antagonists as the canine parietal cell receptor. Gastrin-stimulated phosphatidylinositol hydrolysis and intracellular Ca2+ mobilization in COS-7 cells expressing the cloned receptor suggest second-messenger signaling through phospholipase C. Affinity labeling of the expressed receptor in COS-7 cells revealed a protein identical in size to the native parietal cell receptor. Gastrin receptor transcripts were identified by high-stringency RNA blot analysis in both parietal cells and cerebral cortex, suggesting that the gastrin and CCK-B receptors are either highly homologous or identical.

Original languageEnglish (US)
Pages (from-to)3605-3609
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume89
Issue number8
DOIs
StatePublished - 1992

Keywords

  • G protein-coupled receptor
  • cholecystokinin
  • gastric mucosa

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Expression cloning and characterization of the canine parietal cell gastrin receptor'. Together they form a unique fingerprint.

  • Cite this