Miller T B, Ross C R
J Pharmacol Exp Ther. 1976 Mar;196(3):771-7.
The accumulation of organic cations and anions by the isolated rabbit choroid plexus was measured and the results were considered in comparison to in vivo measurements of transport using the ventriculocisternal perfusion technique also in rabbits. The accumulation in vitro of 3H-p-aminohippurate (PAH) and 14C-N1-methylnicotinamide (NMN) was shown to be organic anion and cation specific and dependent upon oxidative metabolism since tissue/medium ratios were reduced by competitive inhibitors including dibenamine and mepiperphenidol for cation transport and probenecid for anion transport and were also reduced by cyanide and dinitrophenol. Rabbits pretreated with chlorpromazine and anesthetized with pentobarbital were perfused lateral ventricle to cisterna magna with artificial cerebrospinal fluid containing inulin, 3H-PAH and 14C-NMN. Ratios of concentrations of these substances in the perfusate to those infused were calculated. Significant reductions in the ratios for PAH and NMN compared to unulin were obtained when low rates of perfusion, 40mul/min, were employed with low concentrations of PAH (2 mug/ml) and NMN (0.2 mug/ml). Probenecid (10(-3)M) specifically increased the ratio for PAH without affecting the NMN ratios. Mepiperhenidol (10(-o) M) blocked NMN transport but no PAH. The data and calculated clearances indicate that these prototype anions and cations may be actively transported out of cerebrospinal fluid, but for cations only at a low rate.
测定了离体兔脉络丛对有机阳离子和阴离子的蓄积情况,并将结果与同样在兔身上使用脑室池灌注技术进行的体内转运测量结果进行了比较。结果表明,3H-对氨基马尿酸(PAH)和14C-N1-甲基烟酰胺(NMN)在体外的蓄积具有有机阴离子和阳离子特异性,且依赖于氧化代谢,因为组织/培养基比值会被竞争性抑制剂降低,包括用于阳离子转运的二苯那明和哌泊芬地尔以及用于阴离子转运的丙磺舒,同时也会被氰化物和二硝基苯酚降低。用氯丙嗪预处理并用戊巴比妥麻醉的兔子,用含有菊粉、3H-PAH和14C-NMN的人工脑脊液从侧脑室灌注到脑大池。计算了灌注液中这些物质的浓度与注入浓度的比值。当以40微升/分钟的低灌注速率、低浓度的PAH(2微克/毫升)和NMN(0.2微克/毫升)进行灌注时,与菊粉相比,PAH和NMN的比值显著降低。丙磺舒(10^(-3)M)特异性地增加了PAH的比值,而不影响NMN的比值。哌泊芬地尔(10^(-6)M)阻断了NMN的转运,但不影响PAH。数据和计算出的清除率表明,这些原型阴离子和阳离子可能会被主动转运出脑脊液,但对于阳离子来说,转运速率较低。