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Kinetics and sodium independence of [3H]-tiazofurin blood to brain transport in the guinea pig. 1996

Z B Redzic, and I D Markovic, and S S Jovanovic, and J M Gasic, and D M Mitrovic, and B V Zlokovics, and L M Rakic
Institute of Biochemistry, School of Medicine, Belgrade, Yugoslavia.

Tiazofurin is a nucleoside analog with potent antitumor activity. The objective of this study was to define the kinetic parameters of tiazofurin transport from blood into the guinea pig brain. The second aim was to define kinetic parameters of tiazofurin transport inhibition by adenosine (Ki and Kda), as well as whether tiazofurin blood-to-brain transport was performed in countertransport with Na+. In order to determine these parameters, the in situ method of perfusion of guinea pig brain was used. Addition of increasing concentrations of unlabelled tiazofurin to perfusing medium (0.05-2.7 mmol/l) caused progressive decrease of [3H]-tiazofurin brain clearance with Km values ranging from 119.57 +/- 40.12 to 150.17 +/- 51.68 x 10(-6) mol/l. Maximal transport capacity ranged from 325.03 +/- 113.93 to 417.50 +/- 151.53 pmol/min/g. Introduction of adenosine into the perfusing medium (0.005-0.2 mmol/l) caused similar but more rapid decrease of [3H]-tiazofurin brain clearance (Ki = 6.36 +/- 3.14 x 10(-6) mol/l for nucleus caudate and 11.74 +/- 4.85 x 10(-6) mol/l for cerebral cortex). Therefore, it seems that transport system for adenosine plays the main role in tiazofurin brain uptake, but another transport mechanism is also involved in this process. Depletion of perfusing medium from sodium ions did not cause significant change in volume of distribution values for [3H]-tiazofurin in guinea pig cerebral cortex.

UI MeSH Term Description Entries
D007553 Isotope Labeling Techniques for labeling a substance with a stable or radioactive isotope. It is not used for articles involving labeled substances unless the methods of labeling are substantively discussed. Tracers that may be labeled include chemical substances, cells, or microorganisms. Isotope Labeling, Stable,Isotope-Coded Affinity Tagging,Isotopically-Coded Affinity Tagging,Affinity Tagging, Isotope-Coded,Affinity Tagging, Isotopically-Coded,Isotope Coded Affinity Tagging,Labeling, Isotope,Labeling, Stable Isotope,Stable Isotope Labeling,Tagging, Isotope-Coded Affinity,Tagging, Isotopically-Coded Affinity
D008962 Models, Theoretical Theoretical representations that simulate the behavior or activity of systems, processes, or phenomena. They include the use of mathematical equations, computers, and other electronic equipment. Experimental Model,Experimental Models,Mathematical Model,Model, Experimental,Models (Theoretical),Models, Experimental,Models, Theoretic,Theoretical Study,Mathematical Models,Model (Theoretical),Model, Mathematical,Model, Theoretical,Models, Mathematical,Studies, Theoretical,Study, Theoretical,Theoretical Model,Theoretical Models,Theoretical Studies
D010477 Perfusion Treatment process involving the injection of fluid into an organ or tissue. Perfusions
D001812 Blood-Brain Barrier Specialized non-fenestrated tightly-joined ENDOTHELIAL CELLS with TIGHT JUNCTIONS that form a transport barrier for certain substances between the cerebral capillaries and the BRAIN tissue. Brain-Blood Barrier,Hemato-Encephalic Barrier,Barrier, Blood-Brain,Barrier, Brain-Blood,Barrier, Hemato-Encephalic,Barriers, Blood-Brain,Barriers, Brain-Blood,Barriers, Hemato-Encephalic,Blood Brain Barrier,Blood-Brain Barriers,Brain Blood Barrier,Brain-Blood Barriers,Hemato Encephalic Barrier,Hemato-Encephalic Barriers
D002421 Caudate Nucleus Elongated gray mass of the neostriatum located adjacent to the lateral ventricle of the brain. Caudatus,Nucleus Caudatus,Caudatus, Nucleus,Nucleus, Caudate
D002540 Cerebral Cortex The thin layer of GRAY MATTER on the surface of the CEREBRAL HEMISPHERES that develops from the TELENCEPHALON and folds into gyri and sulci. It reaches its highest development in humans and is responsible for intellectual faculties and higher mental functions. Allocortex,Archipallium,Cortex Cerebri,Cortical Plate,Paleocortex,Periallocortex,Allocortices,Archipalliums,Cerebral Cortices,Cortex Cerebrus,Cortex, Cerebral,Cortical Plates,Paleocortices,Periallocortices,Plate, Cortical
D006168 Guinea Pigs A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea
D000241 Adenosine A nucleoside that is composed of ADENINE and D-RIBOSE. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. Adenocard,Adenoscan
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000970 Antineoplastic Agents Substances that inhibit or prevent the proliferation of NEOPLASMS. Anticancer Agent,Antineoplastic,Antineoplastic Agent,Antineoplastic Drug,Antitumor Agent,Antitumor Drug,Cancer Chemotherapy Agent,Cancer Chemotherapy Drug,Anticancer Agents,Antineoplastic Drugs,Antineoplastics,Antitumor Agents,Antitumor Drugs,Cancer Chemotherapy Agents,Cancer Chemotherapy Drugs,Chemotherapeutic Anticancer Agents,Chemotherapeutic Anticancer Drug,Agent, Anticancer,Agent, Antineoplastic,Agent, Antitumor,Agent, Cancer Chemotherapy,Agents, Anticancer,Agents, Antineoplastic,Agents, Antitumor,Agents, Cancer Chemotherapy,Agents, Chemotherapeutic Anticancer,Chemotherapy Agent, Cancer,Chemotherapy Agents, Cancer,Chemotherapy Drug, Cancer,Chemotherapy Drugs, Cancer,Drug, Antineoplastic,Drug, Antitumor,Drug, Cancer Chemotherapy,Drug, Chemotherapeutic Anticancer,Drugs, Antineoplastic,Drugs, Antitumor,Drugs, Cancer Chemotherapy

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