Cholecystokinin and gastrin receptors (CCK1R and CCK2R) are G protein-coupled receptors that have been the subject of intensive research in the last 10 years with corresponding advances in the understanding of their functioning and physiology. In this review, we first describe general properties of the receptors, such as the different signaling pathways used to exert short- and long-term effects and the structural data that explain their binding properties, activation, and regulation. We then focus on peripheral cholecystokinin receptors by describing their tissue distribution and physiological actions. Finally, pathophysiological peripheral actions of cholecystokinin receptors and their relevance in clinical disorders are reviewed.

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The association of bone morphogenetic proteins (BMPs) with calcium phosphate bioceramics is known to confer them osteoinductive properties. The aim of this study was to evaluate the surface properties, especially regarding recombinant human BMP-2 (rhBMP-2) adsorption and release, of commercial sintered biphasic calcium phosphate ceramics after coating with biomimetic nanocrystalline apatite. The raw and coated ceramics exhibited similar macroporous structures but different nanometer-sized pores contents. Both types of ceramics showed Langmuir-type adsorption isotherms of rhBMP-2. The coating noticeably increased the rate of adsorption and the total amount of growth factor taken up, but the maximum coverage per surface area unit as well as the affinity constant appeared lower for coated ceramics compared with raw ceramic surfaces. The limited advantage gained by coating the ceramics can be assigned to a lower accessibility of the surface adsorption sites compared with the raw ceramics. The quantity of rhBMP-2 spontaneously released in cell culture medium during the first weeks was lower for coated samples than for uncoated ceramics and represented a minor fraction of the total adsorbed amount. In conclusion, the nanocrystalline apatite coating was found to favor the adsorption of rhBMP-2 while providing a mean to fine tune the release of the growth factor.

Therapeutic strategies using drugs which cause Lysosomal Cell Death have been proposed for eradication of resistant cancer cells. In this context, nanotherapy based on Magnetic Intra-Lysosomal Hyperthermia (MILH) generated by magnetic nanoparticles (MNPs) that are grafted with ligands of receptors overexpressed in tumors appears to be a very promising therapeutic option. However, mechanisms whereby MILH induces cell death are still elusive. Herein, using Gastrin-grafted MNPs specifically delivered to lysosomes of tumor cells from different cancers, we provide evidences that MILH causes cell death through a non-apoptotic signaling pathway. The mechanism of cell death involves a local temperature elevation at the nanoparticle periphery which enhances the production of reactive oxygen species through the lysosomal Fenton reaction. Subsequently, MILH induces lipid peroxidation, lysosomal membrane permeabilization and leakage of lysosomal enzymes into the cytosol, including Cathepsin-B which activates Caspase-1 but not apoptotic Caspase-3. These data highlight the clear potential of MILH for the eradication of tumors overexpressing receptors.

The cholecystokinin (CCK) receptor-1 (CCK1R) is a G protein-coupled receptor, which mediates important central and peripheral cholecystokinin actions. Our aim was to progress in mapping of the CCK1R binding site by identifying residues that interact with the methionine and phenylalanine residues of the C-terminal moiety of CCK because these are crucial for its binding and These new and important insights will serve to better understand the activation process of CCK1R and to design or optimize ligands.

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