Analysis of variation in L‐365,260 competition curves in radioligand binding assays

Analysis of the variation in the action of L‐365,260 at CCKB/gastrin receptors in rat, guinea‐pig and mouse isolated gastric tissue assays

“…The L-365,260 affinity estimates at the inferred receptor subtypes are indistinguishable from those we obtained in a similar analysis of the behaviour of L-365,260 in CCKB/gastrin receptor radioligand binding experiments in guinea-pig gastric gland and mouse and rat cerebral cortex preparations (Harper et al, 1996). The relationship between our data, the results obtained by other groups who have quantified the activity of L-365,260 in a number of different bioassays and the molecular biological characterization of CCKB/gastrin receptors are considered in the accompanying paper (Harper et al, 1996).…”

“…The relationship between our data, the results obtained by other groups who have quantified the activity of L-365,260 in a number of different bioassays and the molecular biological characterization of CCKB/gastrin receptors are considered in the accompanying paper (Harper et al, 1996). …”

“…However, the reproducibility of the rat stomach data, where the highest concentrations of the compound were used, and the mouse cortex radioligand binding assay data (Harper et al, 1996) suggests that its limited aqueous solubility was not responsible for the data complexity.…”

“…To the second danger, we simply claim that we have been confronted with a degree of variation among the data sets that, in our opinion, could not be ignored. We chose to consider receptor heterogeneity as a possible source of this variation not only because of the systematic nature of the variation but also because we obtained further evidence of receptor heterogeneity in CCKB/ gastrin receptor radioligand binding assays performed over the same time period (Harper et al, 1996).…”

Cholecystokinin antagonists: Pharmacological and therapeutic potential

“…18 Competition radioligand binding studies with diverse CCK 2 receptor antagonists have provided evidence for the existence of two binding sites, or binding states, for this receptor subtype in gastric glands and cortex of some animal species. [68][69][70] Furthermore, the distinct behavioral responses elicited by the CCK 2 selective agonists BC 197 (anxiogenic) and CB 264 (nonanxiogenic and increases memory and attention) have been also related with the existence of two different binding states of these receptors in the brain. 71,72 …”