Aluminum citrate is transported from brain into blood via the monocarboxylic acid transporter located at the blood-brain barrier

被引:31
作者
Ackley, DC
Yokel, RA
机构
[1] UNIV KENTUCKY,MED CTR,COLL PHARM,LEXINGTON,KY 40536
[2] UNIV KENTUCKY,GRAD CTR TOXICOL,LEXINGTON,KY 40536
关键词
aluminum citrate; monocarboxylic acid transporter; blood-brain barrier; microdialysis; transport;
D O I
10.1016/S0300-483X(97)03640-8
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Aluminum citrate transport across the blood-brain barrier was assessed in rats by in vivo microdialysis. Microdialysis probes implanted in the jugular vein as well as the left and right frontal It were demonstrated previously (Alien et al., 1995), in this study, that the steady-state aluminum citrate brain-to-blood-ratio was (BBr) is less than 1, suggesting the presence of a process other than diffusion. The addition of 2,4-dinitrophenol (10 mu M) to the dialysate perfusing a microdialysis probe in the brain increased the steady-state aluminum citrate brain-to-blood-ratio to a value (1.14) not significantly different from 1, suggesting the presence of an active transporter that is blocked by the metabolic inhibitor. The addition of valproic and pyruvic acid, as putative and known substrates for the monocarboxylic acid transporter, respectively, to brain dialysate (10 and 100 mM) had different outcomes, Valproic acid was ineffective at either concentration, whereas pyruvic acid (100 mM) significantly increased the aluminum citrate brain-to-blood-ratio from 0.19 to 0.31. Pyruvic acid (1 M in the dialysate) increased the aluminum citrate brain-to-blood-ratio to a value not different from unity, suggesting competition between aluminum citrate and pyruvic acid for transport. The only energy-dependent, pyruvic acid-inhibitable transporter is the monocarboxylic acid transporter. Theoretical, pharmacokinetic modeling suggests that the transporter producing an aluminum citrate brain-to-blood-ratio less than 1 is predominantly located at the blood-brain barrier, rather than at neuronal or glial cell membranes. We propose that the monocarboxylic acid transporter at the blood-brain barrier maintains a steady-state aluminum citrate brain-to-blood-ratio much less than 1. (C) 1997 Elsevier Science Ireland Ltd.
引用
收藏
页码:89 / 97
页数:9
相关论文
共 32 条
[1]  
Adkison KDK, 1996, J PHARMACOL EXP THER, V276, P1189
[2]   DISTRIBUTION OF UNSATURATED METABOLITES OF VALPROATE IN HUMAN AND RAT-BRAIN - PHARMACOLOGICAL RELEVANCE [J].
ADKISON, KDK ;
OJEMANN, GA ;
RAPPORT, RL ;
DILLS, RL ;
SHEN, DD .
EPILEPSIA, 1995, 36 (08) :772-782
[3]   4-TRIMETHYLAMMONIUM ANTIPYRINE - A QUATERNARY AMMONIUM NONRADIONUCLIDE MARKER FOR BLOOD-BRAIN-BARRIER INTEGRITY DURING INVIVO MICRODIALYSIS [J].
ALLEN, DD ;
CROOKS, PA ;
YOKEL, RA .
JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS, 1992, 28 (03) :129-135
[4]   DISSIMILAR ALUMINUM AND GALLIUM PERMEATION OF THE BLOOD-BRAIN-BARRIER DEMONSTRATED BY INVIVO MICRODIALYSIS [J].
ALLEN, DD ;
YOKEL, RA .
JOURNAL OF NEUROCHEMISTRY, 1992, 58 (03) :903-908
[5]   EVIDENCE FOR ENERGY-DEPENDENT TRANSPORT OF ALUMINUM OUT OF BRAIN EXTRACELLULAR FLUID [J].
ALLEN, DD ;
ORVIG, C ;
YOKEL, RA .
TOXICOLOGY, 1995, 98 (1-3) :31-39
[6]  
Betz A. Lorris, 1994, P681
[7]   ANIMAL-MODELS FOR STUDYING TRANSPORT ACROSS THE BLOOD-BRAIN-BARRIER [J].
BONATE, PL .
JOURNAL OF NEUROSCIENCE METHODS, 1995, 56 (01) :1-15
[8]  
COLLIN AK, 1988, MICRODIALYSIS, P21
[9]   CHARACTERIZATION OF ALPHA-KETO ACID TRANSPORT ACROSS BLOOD-BRAIN-BARRIER IN RATS [J].
CONN, AR ;
FELL, DI ;
STEELE, RD .
AMERICAN JOURNAL OF PHYSIOLOGY, 1983, 245 (03) :E253-E260
[10]   KINETICS OF BLOOD-BRAIN-BARRIER TRANSPORT OF PYRUVATE, LACTATE AND GLUCOSE IN SUCKLING, WEANLING AND ADULT-RATS [J].
CREMER, JE ;
CUNNINGHAM, VJ ;
PARDRIDGE, WM ;
BRAUN, LD ;
OLDENDORF, WH .
JOURNAL OF NEUROCHEMISTRY, 1979, 33 (02) :439-445