Zallakian M, Knoth J, Metropoulos G E, Njus D
Biochemistry. 1982 Mar 2;21(5):1051-5. doi: 10.1021/bi00534a035.
The tranquilizer reserpine has several effects on adrenal medullary chromaffin-granule membrane vesicles (ghosts). At low concentrations (0.20 +/0 0.12 nmol/mg of membrane protein), reserpine inhibits proton-linked epinephrine uptake but does not affect transmembrane pH and electrical potential gradients. Reserpine apparently binds to and blocks the catecholamine translocator. At intermediate concentrations (14.3 +/- 4.8 nmol/mg of membrane protein), reserpine abolishes the ATP-dependent enhancement of 8-anilinonaphthalene-1-sulfonate fluorescence without affecting the ATP-dependent membrane potential. At high concentrations (550 +/- 390 nmol/mg of membrane protein), reserpine stimulates the efflux of epinephrine from preloaded chromaffin-granule ghosts. Because it is highly hydrophobic, reserpine partitions into the membrane and probably exerts a nonspecific detergent-like action. At high concentrations (74 +/- 25 nmol/mg of lipid), reserpine also increases the permeability of phospholipid vesicles to epinephrine. The effectiveness of reserpine in inhibiting epinephrine transport correlates with the reserpine/membrane ratio but not with the molar concentration. This may account for the larger variation in reports of effective reserpine concentrations.
镇静剂利血平对肾上腺髓质嗜铬颗粒膜囊泡（空泡）有多种作用。在低浓度（0.20±0.12纳摩尔/毫克膜蛋白）时，利血平抑制质子偶联的肾上腺素摄取，但不影响跨膜pH和电势梯度。利血平显然与儿茶酚胺转运体结合并阻断它。在中等浓度（14.3±4.8纳摩尔/毫克膜蛋白）时，利血平消除了8-苯胺基萘-1-磺酸盐荧光的ATP依赖性增强，而不影响ATP依赖性膜电位。在高浓度（550±390纳摩尔/毫克膜蛋白）时，利血平刺激预先装载的嗜铬颗粒空泡中肾上腺素的外流。由于利血平高度疏水，它会分配到膜中，并可能发挥类似非特异性去污剂的作用。在高浓度（74±25纳摩尔/毫克脂质）时，利血平还会增加磷脂囊泡对肾上腺素的通透性。利血平抑制肾上腺素转运的有效性与利血平/膜的比例相关，而与摩尔浓度无关。这可能解释了有效利血平浓度报告中较大的差异。
