Effects of cholecystokinin-58 on type 1 cholecystokinin receptor function and regulation

S. Vincent Wu, Kaleeckal G. Harikumar, Rebecca J. Burgess, Joseph R. Reeve, Laurence J. Miller

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Cholecystokinin, like many peptide hormones, is present as multiple molecular forms. CCK-58 has been identified as the dominant form in the circulation, whereas most of the studies of CCK-receptor interactions have been performed with CCK-8. Despite both sharing the pharmacophoric region of CCK, representing its carboxy terminal heptapeptide amide, studies in vivo have demonstrated biological diversity of action of the two peptides, with CCK-58, but not CCK-8, stimulating pancreatic fluid secretion and lengthening the interval between meals. Here, we have directly studied the ability of these two CCK peptides to bind to the type 1 CCK receptor and to stimulate it to elicit an intracellular calcium response. The calcium response relative to receptor occupation was identical for CCK-58 and CCK-8, with the longer peptide binding with approximately fivefold lower affinity. We also examined the ability of the two peptides to elicit receptor internalization using morphological techniques and to disrupt the constitutive oligomerization of the CCK receptor using receptor bioluminescence resonance energy transfer. Here, both full agonist peptides had similar effects on these regulatory processes. These data suggest that both molecular forms of CCK act at the CCK1 receptor quite similarly and elicit similar regulatory processes for that receptor, suggesting that the differences in biological activity observed in vivo most likely reflect differences in the clearance and/or metabolism of these long and short forms of CCK peptides.

Original languageEnglish (US)
Pages (from-to)G641-G647
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume295
Issue number3
DOIs
StatePublished - Sep 2008

Keywords

  • Bioluminescence resonance energy transfer

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

Fingerprint Dive into the research topics of 'Effects of cholecystokinin-58 on type 1 cholecystokinin receptor function and regulation'. Together they form a unique fingerprint.

  • Cite this