Characterisation of central adenosine A(1) receptors and adenosine transporters in mice lacking the adenosine A(2a) receptor

The present study was designed to assess whether adenosine 4(2A) receptor k nockout mice exhibit altered purine utilisation in brain nuclei. Specifical ly, the properties of adenosine transporters and adenosine A(1) receptors w ere characterised in brain membranes and on slide-mounted sections. The B-M AX for [H-3]nitrobenzylthioinosine ([H-3]NBTI) binding (adenosine transport er 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 fmo l/mg protein). Quantitative autoradiography data indicated that [H-3]NBTI b inding in the medulla oblongata of heterozygous mice was seen to decrease s ignificantly (P<0.05) in the subpostremal nucleus tractus solitarius (NTS), medial NTS, inferior olive and area postrema (AP). On the other hand, in t he homozygous mice a decrease was seen in the medial NTS and AP. In the pen s, [H-3]1,3-dipropyl-8-cyclopentylxanthine ([H-3]DPCPX) (adenosine A(1) rec eptor density) binding increased significantly (P<0.05, Kruskal-Wallis ANOV A) in the lateral parabrachial nucleus, caudal pontine reticular nucleus an d locus coeruleus of homozygotes compared to wildtype. In higher brain cent res, [H-3]NBTI binding was reduced in the paraventricular thalamic nucleus of both heterozygous and homozygous mice. whereas [H-3]DPCPX binding was re duced in the hippocampus and lateral hypothalamus of heterozygotes. In homo zygotes, [H-3]DPCPX binding in the hippocampus increased compared to wildty pe mice. The present study indicates that deletion of the A(2a) receptor ma y have contributed to region-specific compensatory changes in purine utilis ation in brain nuclei associated with autonomic, neuroendocrine and behavio ural regulation. (C) 2000 Elsevier Science B.V. All rights reserved.