In vitro characterization of radioiodinated (-)-m-iodovesamicol in rat cerebral membranes.
We investigated the binding characteristics of 125I-(-)-m-iodovesamicol (125I-(-)-mIV), radioiodinated at the meta position of the 4-phenylpiperidine moiety, in cerebral membranes of the rat brain. The receptor binding affinity of (-)-mIV (Ki = 37 nM) was comparable to that of (-)-vesamicol (Ki = 30 nM). The stereoselectivity of (-)-mIV and (-)-vesamicol for the vesamicol receptor was very high [both (-)-mIV and (-)-vesamicol binding more than 20-fold more active than their (+)isomers], and 125I-(-)-mIV had low affinity for the sigma, dopamine, serotonin, adrenaline and acetylcholine receptors. Furthermore, in a saturation binding study using cerebral membrane preparations, (-)-mIV exhibited a Kd of 18.2 nM with maximum number of binding site Bmax of 660 fmol/mg of protein. These results showed that the characteristics of binding between (-)-mIV and (-)-vesamicol to cholinergic binding sites in the rat brain were similar.
Shiba
K
K
Radioisotope Center, School of Medicine, Kanazawa University, Japan.
Mori
H
H
Ichikawa
A
A
Tonami
N
N
D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D007457:Iodine Radioisotopes; D008297:Male; D009467:Neuromuscular Depolarizing Agents / Q000378:metabolism*; D010880:Piperidines / Q000378:metabolism*; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley
D007457:Iodine Radioisotopes; D009467:Neuromuscular Depolarizing Agents; D010880:Piperidines; C006189:vesamicol