Characterization of radioiodinated (-)-ortho-iodovesamicol binding in rat brain preparations.
We investigated the binding characteristics of optical isomers of three iodovesamicol analogs to vesicular acetylcholine transporters (VAChT) and to sigma receptors (sigma-1, sigma-2) in rat brains. In competitive inhibition studies, (-)-enantiomers [(-)-ortho-iodovesamicol ((-)-oIV), (-)-meta-iodovesamicol ((-)-mIV), (-)-vesamicol] displayed a higher affinity for VAChT than (+)-enantiomer [(+)-oIV, (+)-mIV, (+)-vesamicol]. (-)-oIV and (-)-mIV showed the same high affinity for VAChT as (-)-vesamicol. For sigma receptors(sigma-1, sigma-2), (-)-oIV (Ki = 62.2 nM (to sigma-1) and 554 nM(to sigma-2)) showed a lower affinity than (-)-mIV (Ki = 4.5 nM (to sigma-1) and 42.9 nM (to sigma-2)). Furthermore, in a saturation binding study, (-)-[125I]-oIV exhibited a Kd of 17.4 +/- 5.1 nM with a maximum number of binding sites, Bmax, of 559 +/- 51 fmol/ mg of protein. These results showed that (-)-oIV binds to vesicular acetylcholine transporters (VAChT) more selectively than (-)-mIV, previously reported as a VAChT mapping agent, and may be suitable for VAChT imaging studies.
Radioisotope Center, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8640, Ishikawa, Japan. shiba@med.kanazawa-u.ac.jp
Kazuhiro
K
Shiba
Takaya
T
Yano
Wataru
W
Sato
Hirofumi
H
Mori
Norihisa
N
Tonami
D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007425:Intracellular Membranes / Q000378:metabolism; D007457:Iodine Radioisotopes; D008297:Male; D026901:Membrane Transport Proteins; D009467:Neuromuscular Depolarizing Agents / Q000378:metabolism*; D010880:Piperidines / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017480:Receptors, sigma / Q000378:metabolism; D013237:Stereoisomerism; D013347:Subcellular Fractions / Q000378:metabolism; D050494:Vesicular Acetylcholine Transport Proteins; D033921:Vesicular Transport Proteins
D002352:Carrier Proteins; D007457:Iodine Radioisotopes; D026901:Membrane Transport Proteins; D009467:Neuromuscular Depolarizing Agents; D010880:Piperidines; D017480:Receptors, sigma; C493461:Slc18a3 protein, rat; D050494:Vesicular Acetylcholine Transport Proteins; D033921:Vesicular Transport Proteins; C006189:vesamicol