Comparison of the binding of optically pure (?)- and (+)-[3H]nicotine to rat brain membranes

Abstract

A comparison of the binding of (-)- and (+)-[3H]nicotine to rat brain membranes revealed that only the (-)-enantiomer showed high affinity binding; while the (+)-enantiomer was at least 1/10 as effective as the (-)-enantiomer when in competition with (-)-[3H]nicotine as the ligand. Positive cooperativity, which is observed with (-)-[3H]nicotine in the presence of low concentrations of (+)-nicotine, may account for the seeming paradox.

α‐Bungarotoxin Binds to Low‐Affinity Nicotine Binding Sites in Rat Brain

“…These observations agree with the findings of Marks and Collins (1982) for t3H]nicotine binding to mouse brain. Similar KD values for a high-affinity site in rat brain have been reported (Romano and Goldstein, 1980; Sershen et al, 198 1; Costa and Murphy, 1983; Hayashi et al, 1984; London et al, 1985), although other workers have found higher affinities (Yoshida et al, 1982; Clarke et al, 1984; Sloan et al, 1984;Abood et al, 1985; Benwell and Balfour, 1985). Analysis of the inhibition of [3H]nicotine binding by unlabelled nicotine over a greater concentration range ( 10-3-10-'0 M ) resulted in a Ki value for (-)-nicotine of 6 X M(Tab1e 2), which is in reasonable agreement with the apparent KD.…”

“…Marks and Collins (1 982) suggested that (+)-nicotine binds almost exclusively to the low-affinity site. In a recent comparison of the binding of the tritiated enantiomers of nicotine to rat brain membranes, Abood et al (1985) found that (-)-[3H]nicotine labelled two sites with nanomolar or subnanomolar affinities, whereas (+)-[3H]nicotine did not exhibit any high-affinity specific binding at physiological pH. (At pH 8.5, the unnatural enantiomer labelled one site with nanomolar affinity.)…”

“…(At pH 8.5, the unnatural enantiomer labelled one site with nanomolar affinity.) However, a complex interaction between the enantiomers, resembling positive cooperativity at the high-affinity binding site, has been described (Sloan et al, 1984;Abood et al, 1985).…”

Application of carbon-11 labelled nicotine in the measurement of human cerebral blood flow and other physiological parameters

“…Nicotine is not only a ligand tracer exhibiting affinity to acetylcholine-nicotinic receptors in brain, but also an excellent tracer for measuring CBF (Ohno et al 1979;Suzuki et al 1983;Tomida et al 1987Tomida et al , 1989. The 3H-labelled (S)-(-)enantiomer of nicotine showed high affinity of binding to the membrane of acetylcholine-nicotinic receptor cells in rat brain, while specific binding of 3H-labelled (R)-( + )nicotine is not found at pH 7.5 (Abood et al 1985). If 11C-labelled (S)-nicotine is used as a tracer, it is distributed in three compart- merits, i.e.…”

“…Lastly, 3H-nicotine was found to be an excellent diffusion tracer for measurement of CBF (Ohno et al 1979;Suzuki et al 1983;Tomida et al 1987Tomida et al , 1989 because the brain uptake index (BUI) for nicotine is higher than that for water (Bradbury et al 1975). Prior to the attempt to assay specific binding of l~C-(S)nicotine, which binds to nicotinic receptors in human brain, we used t 1C_(R)nicotine, which does not bind to nicotinic receptors (Abood et al 1985), as a diffusion tracer to measure CBF in normal volunteers and to compare CBF values obtained with 11C-(R)nicotine by means of PET with CBF values obtained using the C 150 2 inhalation steadystate method (Frackowiak et al 1980).…”