Kawai R, Sawada Y, Channing M, Newman A H, Rice K C, Blasberg R G
Nuclear Medicine PET Section, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Bethesda, Maryland 20892.
Am J Physiol. 1990 Oct;259(4 Pt 2):H1278-87. doi: 10.1152/ajpheart.1990.259.4.H1278.
The "rapid-phase" brain distribution of 3H-labeled enantiomers of the opiate receptor antagonist cyclofoxy (CF), receptor active (-) and inert (+) forms, was measured during 20- to 180-s intravenous infusion in rats. [14C]iodoantipyrine was coinfused during these experiments to obtain a simultaneous measure of blood flow. The influx clearance (K1) across the blood-brain barrier (BBB) and the rapid binding equilibrium constant (Keq) were estimated in different brain regions for both enantiomers (2-compartmental model); a possible receptor binding process (k3) was also examined for (-)-CF (3-compartment model). K1 (0.46-0.91 ml.min-1.g-1), the capillary permeability-surface area product (PS; 0.75 approximately 1.4 ml.min-1.g-1) and the tissue extraction fraction (E; 0.6-0.7) were found to be identical for both enantiomers in the nonreceptor binding model; Keq was identical in cerebellum but larger for (-)-CF in other brain structures. The difference in Keq between the enantiomers (2-compartment model) correlated with the rank order of opiate receptor density observed in vitro and in vivo. These results suggest that concomitant use of (-)-CF and (+)-CF will be useful for in vivo receptor binding analyses.
在大鼠静脉注射20至180秒期间，测定了阿片受体拮抗剂环福新（CF）的3H标记对映体（受体活性（-）和惰性（+）形式）的“快速相”脑分布。在这些实验中，同时注射[14C]碘安替比林以同步测量血流量。对于两种对映体，在不同脑区估计了穿过血脑屏障（BBB）的流入清除率（K1）和快速结合平衡常数（Keq）（二室模型）；还针对（-）-CF研究了可能的受体结合过程（k3）（三室模型）。在非受体结合模型中，发现两种对映体的K1（0.46 - 0.91 ml·min-1·g-1）、毛细血管通透性-表面积乘积（PS；约0.75 - 1.4 ml·min-1·g-1）和组织提取分数（E；0.6 - 0.7）相同；在小脑中Keq相同，但在其他脑结构中（-）-CF的Keq更大。对映体之间Keq的差异（二室模型）与体外和体内观察到的阿片受体密度的等级顺序相关。这些结果表明，同时使用（-）-CF和（+）-CF将有助于体内受体结合分析。
