Differential alterations in adenosine A1 and kappa 1 opioid receptors in the striatum in Alzheimer's disease.
The alterations in Alzheimer's disease (AD) of two binding sites in the striatum suggested to have a presynaptic localisation have been investigated by quantitative ligand binding autoradiography. Adenosine A1 binding sites labelled with [3H]cyclohexyladenosine (CHA) and kappa 1 opioid binding sites labelled with [3H]U-69593 were studied in adjacent sections of the striatum obtained postmortem from 10 patients with AD and 9 matched controls. In AD, there was a significant reduction of [3H]CHA binding sites in the caudate nucleus (control = 88 +/- 4; AD = 56 +/- 6 pmol/g tissue; mean +/- S.E.M.) and putamen (control = 83 +/- 4; AD = 58 +/- 7 pmol/g). In control subjects, highest levels of [3H]U-69593 binding were localised to patches within the caudate nucleus (9.66 +/- 0.58 pmol/g) with lower levels in the matrix (5.54 +/- 0.48 pmol/g). There was no alteration in [3H]U-69593 binding sites in either the caudate nucleus (patches and matrix) or putamen of AD patients. The activity of choline acetyltransferase (ChAT), determined in the same tissue samples used for autoradiographic analysis, was significantly reduced in AD (control = 124 +/- 11; AD = 64 +/- 14 nmol/h/mg protein). There was a positive correlation between ChAT activity and [3H]CHA binding (r = 0.769), but not [3H]U-69593 binding (r = 0.197). The results indicate that a marked loss of adenosine A1 receptors occurs in the striatum of AD with no loss of kappa 1 opioid receptors, and that the loss of A1 receptors parallels the loss of choline acetyltransferase activity.
Ikeda
M
M
Wellcome Surgical Institute & Hugh Fraser Neuroscience Labs, University of Glasgow, UK.
Mackay
K B
KB
Dewar
D
D
McCulloch
J
J
D000241:Adenosine / Q000031:analogs & derivatives / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D000700:Analgesics / Q000378:metabolism; D001344:Autopsy; D001345:Autoradiography; D044482:Benzeneacetamides; D002421:Caudate Nucleus / Q000378:metabolism / Q000473:pathology; D002795:Choline O-Acetyltransferase / Q000032:analysis / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011699:Putamen / Q000378:metabolism; D011759:Pyrrolidines / Q000378:metabolism; D017473:Receptors, Opioid, kappa / Q000378:metabolism*; D011983:Receptors, Purinergic / Q000378:metabolism*; D012016:Reference Values; D014316:Tritium
D000700:Analgesics; D044482:Benzeneacetamides; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D011983:Receptors, Purinergic; D014316:Tritium; C027513:N(6)-cyclohexyladenosine; D002795:Choline O-Acetyltransferase; C045444:U 69593; D000241:Adenosine