Uptake of valproic acid into rat brain is mediated by a medium-chain fatty acid transporter.
Uptake of valproic acid into rat brain is mediated by a medium-chain fatty acid transporter.
复制标题
DOI：
--
复制
发表时间：
1996-03
期刊：
影响因子：
--
通讯作者：
K. Adkison;D. Shen
中科院分区：
文献类型：
--
作者：
K. Adkison;D. Shen
用“原位”脑灌流技术研究了丙戊酸(VPA)在大鼠脑内不同区域的摄取。VPA的摄取动力学表现为部分饱和和反式刺激，表明载体介导的转运和扩散同时存在。可饱和突起的表观米氏常数范围为皮质10 mm至丘脑23.5 mm。短链(~lt；/-C4)脂肪酸和α-酮酸共灌流不抑制放射性示踪剂VPA的摄取，提示血脑屏障上的短链单羧酸载体不参与VPA的摄取。相反，中链(C6-C12)脂肪酸抑制放射性示踪剂VPA的摄取。此外，对氨基马尿酸(PAH)可抑制放射性示踪剂VPA的摄取，而顺式和反式中链二羧酸盐均可显著刺激脑组织对VPA的摄取。这些观察结果表明，血脑屏障上的VPA转运体可能是一种阴离子交换器，其工作方式类似于已报道的肾小管上皮基侧膜上的PAH转运体。然而，与PAH的肾基侧转运不同，丙磺舒促进而不是抑制VPA的摄取。此外，二羧酸盐对大脑VPA摄取的刺激似乎不依赖于Na+。VPA对大鼠脑内辛酸摄取有相反的抑制作用。此外，VPA能够抑制大脑对包括醋酸盐、乳酸和丙酮酸在内的短链单羧酸的摄取。
The uptake of valproic acid (VPA) from blood into several brain regions was investigated using the "in situ" brain perfusion technique in the rat. The uptake kinetics of VPA exhibited partial saturability and trans-stimulation, which indicate the simultaneous presence of carrier-mediated transport and diffusion. The apparent Michaelis constant for the saturable process ranged from 10mM in the cortical regions to 23.5 mM in the thalamus. The uptake of radiotracer VPA was not inhibited by coperfusion of short-chain (</-C4) fatty acids and alpha-keto acids, which suggests that the short-chain monocarboxylic acid carrier at the blood-brain barrier is not involved in the uptake of VPA. In contrast, medium-chain (C6-C12) fatty acids inhibited the uptake of radiotracer VPA. In addition, para-aminohippurate (PAH) inhibited, whereas both cis- and trans-presence of medium-chain dicarboxylates markedly stimulated the cerebral uptake of radiotracer VPA. These observations suggest that the putative VPA transporter at the blood-brain barrier may be an anion exchanger that operates in a manner similar to that reported for the PAH transporter at the basolateral membrane of the renal tubular epithelium. However, unlike renal basolateral transport of PAH, probenecid promoted rather than inhibited VPA uptake. Also, dicarboxylate stimulation of brain VPA uptake does not appear to be Na+ dependent. VPA exerted a reciprocal inhibition of octanoate uptake into rat brain. Moreover, VPA was capable of inhibiting brain uptake of short-chain monocarboxylic acids, including acetate, lactate and pyruvate.