Autoradiographic localization of 5HT2 receptors in rat brain using [125I]-DOI, a selective psychotomimetic radioligand.
1. Binding sites for the R and S enantiomers of the 5HT2 agonist DOI (2,5-dimethoxy-4-iodophenylisopropylamine) were identified in rat brain using quantitative in-vitro autoradiography and compared with [125I]-LSD binding. 2. In most regions of the brain, binding density of the less active isomer [125I]S-DOI was 15 to 85% of that exhibited by the active [125I]R-DOI isomer. 3. Cortical membrane preparations exhibited two binding sites, of the enantiomers with high (KdH) and low (KdL) affinity constants of 1.2 +/- 0.02 nM and 29 +/- 7 nM for the [125I]R-DOI and 2.1 +/- 0.2 nM and 18 +/- 4 nM for [125I]S-DOI respectively. The respective high (BmaxH) and low (BmaxL) binding densities were 92 +/- 10 and 536 +/- 164 fmol/mg protein for the [125I]R-DOI and 67 +/- 19 and 245 +/- 60 fmol/mg protein for [125I]S-DOI. 4. Our results correlate with regional distribution of 5HT2 receptors reported in previous studies and indicate that DOI and its congeners have potential clinical applications for the in-vivo localization of 5HT2 receptors.
Nazarali
A J
AJ
Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, Maryland.
McKenna
D J
DJ
Saavedra
J M
JM
D000662:Amphetamines / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D007457:Iodine Radioisotopes; D007700:Kinetics; D008297:Male; D008566:Membranes / Q000378:metabolism; D009928:Organ Specificity; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000378:metabolism*
D000662:Amphetamines; D007457:Iodine Radioisotopes; D011985:Receptors, Serotonin; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine