Abstract:
:The binding characteristics of [3H]cytisine, a putative CNS nicotinic receptor ligand, were examined in 4 regions of the human brain. [3H]Cytisine was found to bind non-cooperatively with high affinity to a single site in tissue homogenates and to exhibit low non-specific association. The binding characteristics of this ligand were evaluated in thalamus at 4 degrees C and 24 degrees C. The association constants were found to be 0.234 and 0.308 min-1 nM-1, while the dissociation constants were 0.007 and 0.098 min-1, respectively. Saturation analysis of thalamus revealed the equilibrium Kd to be 147 pM (4 degrees C) and 245 pM (24 degrees C), values in good agreement with those determined kinetically. The Hill coefficient varied slightly between brain regions; however, the mean values in all regions examined were close to 1.0 at 0.95 +/- 0.03 (4 degrees C) and 0.91 +/- 0.04 (24 degrees C). [3H]Cytisine binding could be displaced using both nicotinic agonists and antagonists. Cytisine was the most potent displacer of [3H]cytisine binding with an Ki of 250 pM. Nicotine and acetylcholine were also potent displacers with Ki values of 1.8 and 8.1 nM, respectively. The nicotinic antagonists alpha-bungarotoxin and mecamylamine were ineffective competitors for the [3H]cytisine binding site while dihydro-beta-erythroidine had an Ki value of 109 nM. Thalamus showed the highest density of cytisine binding sites of all the regions examined (48 fmol/mg protein) while the hippocampus, cingulate gyrus and the cortex showed Bmax values of 18.9, 19.3 and 8.8 fmol/mg protein, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
journal_name
Brain Resjournal_title
Brain researchauthors
Hall M,Zerbe L,Leonard S,Freedman Rdoi
10.1016/0006-8993(93)90410-osubject
Has Abstractpub_date
1993-01-08 00:00:00pages
127-33issue
1eissn
0006-8993issn
1872-6240pii
0006-8993(93)90410-Ojournal_volume
600pub_type
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