| Autor: |
Little, Karley Y., Kirkman, Jacob A., Carroll, F. Ivy, Breese, George R., Duncan, Gary E. |
| Zdroj: |
Journal of Neurochemistry; December 1993, Vol. 61 Issue: 6 p1996-2006, 11p |
| Abstrakt: |
[125I]RTI‐55 is a newly synthesized cocaine congener that may offer advantages over other ligands previously used to examine cocaine binding sites. However, the in vitro pharmacological and anatomical characterization of [125I]RTI‐55 binding sites has not been previously performed in human brain. To determine the specificity, stability, and feasibility of [125I]RTI‐55 for use in radioligand binding assays in postmortem human tissue, a series of experiments were performed characterizing [125I]RTI‐55 binding sites in human brain using homogenized membrane preparations and quantitative autoradtography. Analysis of the association, dissociation, and saturation data favored two‐phase processes. A curve‐fitting analysis of the data derived in saturation experiments found a high‐affinity site with KD=66 ± 35 pMand Smax= 13.2 ± 10.1 pmol/g of tissue and a low‐affinity site with KD=1.52 ± 0.55 nMand Bmaxof 47.5 ± 11‐2 pmol/g of tissue. Competition by ligands known to bind to the dopamine transporter showed a rank order of RTI‐55 > GBR‐12909 >mazindol > WIN 35428 > = methylphenidate > (−)‐cocaine > buproprion > (±)‐amphetamine. Binding to serotonergic sites was evaluated in the midbrain. Results of the saturation experiment performed autoradiographically in the midbrain showed a single site with KD= 370 ± 84 pM.It appears that [125I]RTI‐55 should be useful in further studies of the regulation of cocaine binding sites using postmortem human specimens. |
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