Characterisation of central adenosine A1 receptors and adenosine transporters in mice lacking the adenosine A2a receptor

被引:21
|
作者
Snell, BJ
Short, JL
Drago, J
Ledent, C
Lawrence, AJ
机构
[1] Monash Univ, Fac Med, Dept Pharmacol, Clayton, Vic 3800, Australia
[2] Monash Med Ctr, Dept Med, Clayton, Vic 3168, Australia
[3] Free Univ Brussels, Fac Med, Inst Rech Interdisciplinaire, Brussels, Belgium
基金
英国医学研究理事会;
关键词
autonomic nervous system; medullary nuclei; pontine nuclei; in vitro autoradiography; saturation binding; up- and down-regulation;
D O I
10.1016/S0006-8993(00)02670-6
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The present study was designed to assess whether adenosine 4(2A) receptor knockout mice exhibit altered purine utilisation in brain nuclei. Specifically, the properties of adenosine transporters and adenosine A(1) receptors were characterised in brain membranes and on slide-mounted sections. The B-MAX for [H-3]nitrobenzylthioinosine ([H-3]NBTI) binding (adenosine transporter density) was significantly reduced in brainstem membranes of homozygotes (560+/-52 fmol/mg protein, n=5, P<0.05, Kruskal-Wallis ANOVA) compared to wildtype (1239+/-213 fmol/mg protein) and heterozygous mice (1300+/-558 fmol/mg protein). Quantitative autoradiography data indicated that [H-3]NBTI binding in the medulla oblongata of heterozygous mice was seen to decrease significantly (P<0.05) in the subpostremal nucleus tractus solitarius (NTS), medial NTS, inferior olive and area postrema (AP). On the other hand, in the homozygous mice a decrease was seen in the medial NTS and AP. In the pens, [H-3]1,3-dipropyl-8-cyclopentylxanthine ([H-3]DPCPX) (adenosine A(1) receptor density) binding increased significantly (P<0.05, Kruskal-Wallis ANOVA) in the lateral parabrachial nucleus, caudal pontine reticular nucleus and locus coeruleus of homozygotes compared to wildtype. In higher brain centres, [H-3]NBTI binding was reduced in the paraventricular thalamic nucleus of both heterozygous and homozygous mice. whereas [H-3]DPCPX binding was reduced in the hippocampus and lateral hypothalamus of heterozygotes. In homozygotes, [H-3]DPCPX binding in the hippocampus increased compared to wildtype mice. The present study indicates that deletion of the A(2a) receptor may have contributed to region-specific compensatory changes in purine utilisation in brain nuclei associated with autonomic, neuroendocrine and behavioural regulation. (C) 2000 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:160 / 169
页数:10
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