Journal
PHARMACOLOGY & THERAPEUTICS
Volume 119, Issue 1, Pages 83-95Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pharmthera.2008.05.001
Keywords
cholecystokinin; gastrin; photoaffinity labeling; GPCR; molecular modeling
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Funding
- NIDDK NIH HHS [DK32878, R37 DK032878, R01 DK032878, R01 DK046577] Funding Source: Medline
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Two structurally-related guanine nucleotide-binding protein-coupled receptors for two related peptides, cholecystokinin (CCK) and gastrin, have evolved to exhibit substantial diversity in specificity of ligand recognition, in their molecular basis of binding these ligands, and in their mechanisms of biochemical and cellular regulation. Consistent with this, the CCK1 and CCK2 receptors also play unique and distinct roles in physiology and pathophysiology. The paradigms for ligand recognition and receptor regulation and function are reviewed in this article, and should be broadly applicable to many members of this remarkable receptor superfamily. This degree of specialization is instructive and provides an encouraging basis for the diversity of potential drugs targeting these receptors and their actions that can be developed. (C) 2008 Elsevier Inc. All rights reserved.
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