Research Project
Grant-in-Aid for Scientific Research (C)
We recently reported that adenine acts as a neurotrophic factor independent of adenosine or P2 receptors in cultured Purkinje cells [Watanabe S., et. al. (2003) J. Neurosci. Res. 74, 754-759], suggesting the presence of specific receptors for adenine in the brain. In this study, the characterization of adenine-binding activity in the rat brain was performed to further characterize the receptor-like adenine-binding sites. Specific binding sites for [3H] adenine were detected in membrane fractions prepared from rat brains. The kinetics of [3H] adenine binding to membranes was described by the association and dissociation rate constants, 8. 6 x 10^5 /M/min and 0.118±0. 045 min-1, respectively. A single binding site for [3H] adenine with a K D of 157. 1±20. 8 nM and a B max of 16. 3 ± 1. 1 pmol/mg protein (n = 6) was demonstrated in saturation experiments. A displacement study involving various related compounds showed that the [3H] adenine binding was highly specific for adenine. It was a … More lso found that [3H] adenine-binding activity was inhibited by adenosine, although other adenosine receptor ligands were ineffective as to [3H] adenine binding. The brain, especially the cerebellum and spinal cord, showed the highest [3H] adenine-binding activity of the tissues examined. These results are consistent with the presence of a novel adenine receptor in rat brain membranes. We examined the effects of various purines on survival in the cerebellar cortex of Purkinje cells with large cell bodies and highly branched dendrites, and it was found that some purine and pyrimidine derivatives influence Purkinje cell survival. Treatment with adenine, guanine, guanosine, guanine nucleotides, and uracil nucleotides protected Purkinje cells from cell death in the cerebellar primary cultures. Among the effective compounds, adenine had the most potent survival activities on Purkinje cells. These results suggest that adenine is involved in the control of Purkinje cell survival in cerebellar primary cultures via a novel adenine-dependent mechanism. Less
All 2008 2007 2006
All Journal Article (18 results) (of which Peer Reviewed: 6 results) Presentation (2 results) Book (1 results)
Bioorg.Med.Chem. 16
Pages: 5039-5049
Chembiochem 2008Mar1(印刷中)
Biochem Pharmacol 75
Pages: 1014-1026
Bioorg Med Chem 1 ; 16(9)
Pages: 5039-49
Chembiochem
Clin Chim Acta
Biochem Pharmacol 1 ; 75(5)
Pages: 1014-26
Cancer Sci 99(3)
Pages: 608-14
10024004105
Chembiochem. (In press)
Clin Chim Acta. (In Press)
Biochem Pharmacol. 75(5)
Pages: 14-26
Bioorg Med Chem
Bioorg Med Chem Lett 1 ; 17(9)
Pages: 2421-4
J Hum Genet
Bioorg Med Chem Lett. 17(9)
Tissue Eng. 12(9)
Glycoconj J. 23(5-6)
Pages: 443-52
Bioorg Med Chem. 14(7)
Pages: 2151-61
