Pharmacological comparison of the alternatively spliced short and long CCK2 receptors.
(1) The alternatively spliced, short and long cholecystokinin receptors (CCK2S and CCK2L) were expressed in NIH3T3 cells, and compared using radioligand-binding assays with identical buffer and incubation conditions. (2) As judged by a saturation analysis, the selective CCK2-receptor antagonist radioligand [3H]-JB93182 did not discriminate between the CCK2S or CCK2L receptors. (3) A global analysis of competition studies, using a range of structurally diverse, CCK-receptor selective ligands, provided further evidence that these receptor subtypes were pharmacologically indistinguishable. However, when analysed individually a number of small, yet significant differences were observed with some of the compounds. (4) These data are consistent with previous study that suggested a possible pharmacological difference between these isoforms, at least in terms of the CCK2-receptor antagonist, L-365,260. However, it would appear that the pharmacological profile of these compounds is not consistent with their affinity at the putative G1/G2 receptors previously described by Harper et al.
Morton
M F
MF
Academic Department of Surgery, GKT Schools of Medicine and Dentistry, King's College, London SE5 9NU. mmorton1@pdus.jnj.com
Harper
E A
EA
Tavares
I A
IA
Shankley
N P
NP
D000818:Animals; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007211:Indoles / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D041681:NIH 3T3 Cells; D011485:Protein Binding; D043887:Receptor, Cholecystokinin B / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*
D007211:Indoles; C109753:JB93182; D043887:Receptor, Cholecystokinin B