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This Article Full Text Full Text (PDF) All Versions of this Article: 295/3/G641    most recent ajpgi.90390.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Wu, S. V. Articles by Miller, L. J. PubMed PubMed Citation Articles by Wu, S. V. Articles by Miller, L. J.

HORMONES AND SIGNALING

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

¹Mayo Clinic, Department of Molecular Pharmacology and Experimental Therapeutics, Scottsdale, Arizona; and ²CURE: Digestive Diseases Research Center, Veterans Affairs Greater Los Angeles Healthcare System, and Digestive Diseases Division, UCLA School of Medicine, Los Angeles, California

Submitted 20 June 2008 ; accepted in final form 28 July 2008

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.

bioluminescence resonance energy transfer