The efflux of purine nucleobases and nucleosides from the rat brain

• Published in: Neuroscience letters 2002-01, Vol.318 (2), p.65-68
• Main Authors: Isakovic, Aleksandra J, Segal, Malcolm B, Milojkovic, Bogdan A, Dacevic, Mirjana P, Misirlic, Sonja T, Rakic, Miodrag L, Redzic, Zoran B
• Format: Article
• Language: English
• Subjects: Adenosine - blood; Adenosine - cerebrospinal fluid; Animals; Biological and medical sciences; Blood-Brain Barrier - drug effects; Blood-Brain Barrier - physiology; Blood–brain barrier; Brain - drug effects; Brain - metabolism; Brain efflux; Carbon Radioisotopes - metabolism; Carrier Proteins - drug effects; Carrier Proteins - physiology; Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges; Deoxyribonucleosides - blood; Deoxyribonucleosides - cerebrospinal fluid; Extracellular Space - drug effects; Extracellular Space - metabolism; Fundamental and applied biological sciences. Psychology; Guanosine - blood; Guanosine - cerebrospinal fluid; Hypoxanthine - blood; Hypoxanthine - cerebrospinal fluid; Injections, Intraventricular; Inosine - blood; Inosine - cerebrospinal fluid; Nucleobases; Nucleosides; Purine Nucleosides - blood; Purine Nucleosides - cerebrospinal fluid; Purine Nucleosides - metabolism; Purines - metabolism; Rats; Rats, Wistar; Transport; Vertebrates: nervous system and sense organs
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/S0304-3940(01)02478-8

The efflux of purine nucleobases and their nucleosides from the rat brain was investigated using the brain efflux index (BEI) method. Calculated BEI values showed that purine nucleobases had very rapid initial efflux after the intracerebral injection, which was followed by the slower efflux due to the intracellular trapping of labelled molecules and confirmed by the capillary depletion technique. The efflux of ribonucleosides was much slower than the efflux of nucleobases and the structure of the sugar moiety seemed to be important, since a significant difference in the efflux velocity between ribo- and deoxyribonucleosides was observed. The results of self- and cross-inhibition studies suggested that the efflux of test molecules was saturable and that purines shared the same transport system on the abluminal side of the blood–brain barrier.