Enhancement of NMDA-induced increases in levels of endogenous adenosine by adenosine deaminase and adenosine transport inhibition in rat striatum

• Published in: Brain research Vol. 702; no. 1; pp. 72 - 76
• Main Authors: Delaney, Suzanne M., Geiger, Jonathan D.
• Format: Journal Article
• Language: English
• Published: London Elsevier B.V 08.12.1995; Amsterdam Elsevier; New York, NY
• Subjects: Adenosine; Adenosine - metabolism; Adenosine Deaminase - metabolism; Animals; Biological and medical sciences; Biological Transport; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Corpus Striatum - metabolism; Deoxycoformycin; Dilazep; Dizocilpine Maleate - pharmacology; Dose-Response Relationship, Drug; Focused microwave sacrifice; Fundamental and applied biological sciences. Psychology; Male; Microinjection; N-Methylaspartate - pharmacology; NMDA; Rats; Rats, Sprague-Dawley; Striatum; Vertebrates: nervous system and sense organs; Striatum; Adenosine; Microinjection; NMDA; Deoxycoformycin; Dilazep; Focused microwave sacrifice; Rat; Enzyme; Biological transport; Rodentia; Central nervous system; Basal ganglion; Corpus striatum; Adenosine deaminase; Vertebrata; Mammalia; Neurotransmitter; Excitatory aminoacid; Hydrolases; Brain (vertebrata)
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/0006-8993(95)01010-9

Unilateral microinjection of N-methyl- d-aspartate (NMDA) into striatum of rats subsequently killed by high-energy focused microwave irradiation significantly increased in vivo levels of endogenous adenosine. At a dose of 25 nmol NMDA, levels of adenosine in injected striata were 263% of levels in uninjected contralateral striata. An inhibitor of adenosine deaminase (deoxycoformycin, DCF) in combination with an inhibitor of adenosine transport (dilazep, DLZP) at a dose that did not affect levels of endogenous adenosine, potentiated NMDA-induced increases in adenosine levels to 426% of contralateral striata. In the presence of DCF and DLZP, NMDA dose-dependently increased levels of adenosine (% of contralateral striatum) from 166% at 10 nmol to 622% at 100 nmol. NMDA-induced increases in levels of endogenous adenosine were completely blocked by prior administration of the NMDA receptor antagonist MK 801 (dizocilpine). Inhibitors of adenosine metabolism and transport may provide therapeutic benefit by potentiating excitatory amino acid-induced increases in levels of endogenous adenosine in vivo.