PT  - JOURNAL ARTICLE
AU  - Knapp, R J
AU  - Vaughn, L K
AU  - Fang, S N
AU  - Bogert, C L
AU  - Yamamura, M S
AU  - Hruby, V J
AU  - Yamamura, H I
TI  - A new, highly selective CCK-B receptor radioligand ([3H][N-methyl-Nle28,31]CCK26-33): evidence for CCK-B receptor heterogeneity.
DP  - 1990 Dec 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1278--1286
VI  - 255
IP  - 3
4099  - http://jpet.aspetjournals.org/content/255/3/1278.short
4100  - http://jpet.aspetjournals.org/content/255/3/1278.full
SO  - J Pharmacol Exp Ther1990 Dec 01; 255
AB  - [N-methyl-Nle28,31]CCK26-33 (SNF 8702) is a nonsulfated cholecystokinin octapeptide analog that is highly selective for cholecystokinin-B (CCK-B) receptors. Inhibition studies using [125I] Bolton-Hunter-labeled CCK-8 show that SNF 8702 has over 4,000-fold greater affinity for CCK receptors in guinea pig cortex relative to those in guinea pig pancreas. SNF 8702 was tritium-labeled to a specific activity of 23.7 Ci/mmol and its binding properties characterized for guinea pig brain membrane preparations. [3H]SNF 8702 binds to a single site with high affinity (Kd = 0.69-0.90 nM) in guinea pig cortex, cerebellum, hippocampus and pons-medulla. Of these four tissues, the highest receptor density was measured in the cortex (86 fmol/mg of protein) and the lowest in the pons-medulla (22 fmol/mg of protein). In contrast to findings of single-site binding in some brain regions, evidence for CCK-B receptor heterogeneity is observed under other conditions. [3H]SNF 8702 binding to membranes prepared from whole guinea pig brain shows biphasic association kinetics at a concentration of 2.0 nM consistent with the presence of binding site heterogeneity. Binding site heterogeneity is consistently observed for [3H]SNF 8702 binding to guinea pig whole brain membranes in saturation studies where a high-affinity site (Kd = 0.31 nM) is distinguished from a low-affinity site (Kd = 3.3 nM). Binding site heterogeneity is also observed for the midbrain-thalamic region. CCK-B receptor heterogeneity is suggested by the effect of the guanyl nucleotide analogue, guanylyl-imidodiphosphate (Gpp(NH)p), on [3H]SNF 8702 binding to CCK-B receptors in the cerebellum.(ABSTRACT TRUNCATED AT 250 WORDS)