Molecular characterization and organ distribution of type A and B cholecystokinin receptors in cynomolgus monkey

Eileen L. Holicky, Elizabeth M. Hadac, Xi Qin Ding, Laurence J Miller

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Differences in the molecular structure or organ distribution of receptors can limit the usefulness of a given species for drug studies. In this work, we have studied cholecystokinin (CCK) receptors in cynomolgus monkey, an animal model useful for preclinical testing. The type A CCK receptor cDNA was cloned and predicted to encode a 428 amino acid peptide that was 98% identical to the human receptor. Only 2 of the 10 residues that were distinct from the human receptor were not present in other cloned CCK receptor species. A Chinese hamster ovary cell line that stably expressed this receptor was developed. The cynomolgus receptor expressed in this environment was functionally indistinguishable from the human receptor, binding CCK with high affinity [inhibition constant (KI) = 1.8 ± 0.5 nM] and exhibiting a potent intracellular calcium signaling response to this hormone (EC50 = 6.6 ± 2.1 pM). Like the human type A CCK receptor, this receptor was expressed prominently in monkey gallbladder and stomach and was expressed in low levels in brain and pancreas. The type B CCK receptor cDNA was cloned from stomach and brain (450 residue receptor that is 96% identical to the human receptor), where it was highly expressed yet was undetectable in gallbladder or pancreas. This work confirms the relevance of the cynomolgus species for preclinical testing of drugs acting on the type A CCK receptor.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume281
Issue number2 44-2
StatePublished - 2001

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Cholecystokinin A Receptor
Cholecystokinin B Receptor
Macaca fascicularis
Cholecystokinin Receptors
Gallbladder
Pancreas
Stomach
Complementary DNA
Calcium Signaling
Brain
Cricetulus
Molecular Structure
Pharmaceutical Preparations
Haplorhini
Ovary
Animal Models
Hormones
Amino Acids
Cell Line
Peptides

Keywords

  • cDNA cloning
  • Cynomolgus monkey
  • G protein-coupled receptor
  • Ligand binding

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology
  • Physiology (medical)

Cite this

Molecular characterization and organ distribution of type A and B cholecystokinin receptors in cynomolgus monkey. / Holicky, Eileen L.; Hadac, Elizabeth M.; Ding, Xi Qin; Miller, Laurence J.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 281, No. 2 44-2, 2001.

Research output: Contribution to journalArticle

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