Cloning and characterization of gastrin receptor from ECL carcinoid tumor of Mastomys natalensis

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Abstract

We report here the cDNA cloning of a putative gastrin receptor from enterochromaffin-like (ECL) carcinoid tumor of Mastomys natalensis. For this study, we used the polymerase chain reaction technique to amplify transmembrane domain sequences related to rat pancreatic cholecystokinin (CCK)-A receptor from the ECL tumor cDNA library. The amino acid sequence deduced from the cloned cDNA showed 85.7% and 49.0% identity to canine parietal cell gastrin receptor and rat pancreatic CCK-A receptor, respectively. Ligand binding studies using COS-7 cells transfected with the cDNA showed the same binding specificity for gastrin and CCK-8 as the gastrin receptor on the Mastomys carcinoid tumor membrane. Both gastrin and CCK-8 elevated free cytosolic calcium concentration in COS-7 cells expressing the cloned receptor. RNA blot analysis revealed the expression of the gastrin receptor in both Mastomys stomach and brain.

References (22)

  • S. Kawabata et al.

    Regul. Pep

    (1991)
  • T. Chiba et al.

    Biochem. Biophys. Res. Commun

    (1991)
  • S. Hosoda et al.

    Biochem. Pharmacol

    (1971)
  • C.S. Chew et al.

    Biochim. Biophys. Acta

    (1986)
  • A.H. Soll et al.

    J. Clin. Invest

    (1984)
  • T. Chiba et al.

    Am. J. Physiol

    (1988)
  • T. Chiba et al.

    Am. J. Physiol

    (1989)
  • A.S. Kopin et al.
  • Y. Tielemans et al.

    Gut

    (1990)
  • A.K. Sandvik et al.

    Am. J. Physiol

    (1991)
  • Y. Inomoto et al.

    Gastroenterology

    (1992)
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    Sequence data from this article have been deposited with the EMBL/GenBank Data Libraries under Accession No. D12817.

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