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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

The cholecystokinin-B receptor antagonist L-740,093 produces an insurmountable antagonism of CCK-4 stimulated functional response in cells expressing the human CCK-B receptor.

A stable cell line expressing the human cholecystokinin-B receptor gene (hCCK-B.CHO) has been employed in an evaluation of the recently developed CCK-B receptor antagonist L-740,093. L-740,093 exhibited high affinity (IC50 0.49 nM) and selectivity (<50% displacement at CCK-A sites at 1 microM) for the human CCK-B receptor subtype as estimated from [125I]-CCK-8S displacement studies with membranes prepared from hCCK-B.CHO cells. The elevation of intracellular free Ca2+ in hCCK-B.CHO cells in response to stimulation with CCK-4 was used to evaluate the antagonist activity of L-740,093 in vitro. L-740,093 potently (IC50 5.4 nM) antagonized the 30 nM CCK-4-stimulated Ca2+ mobilization in hCCK-B.CHO cells. Further studies were performed to investigate the nature of the antagonist activity of L-740,093. When tested at 10 nM L-740,093 produced a modest rightward shift in the CCK-4 dose response curve, an effect which was accompanied by a small reduction (13%) in the maximum response to CCK-4. In the presence of 30 nM L-740,093 the maximum functional response to CCK-4 was further reduced by 45% indicating that L-740,093 behaves as an insurmountable antagonist of the human CCK-B receptor subtype.[1]


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