Up-regulation of striatal adenosine A(2A) receptors in schizophrenia.
Adenosine A (2A) receptors have been implicated in the pathophysiology of schizophrenia by clinical, anatomical, biochemical and genetic studies. We hypothesized that a genetically determined low number of adenosine A (2A) receptors could be a vulnerability factor for the development of the disease. The density of adenosine A (2A) receptors was investigated in human postmortem striatum of patients with schizophrenia (n = 9) and matched controls ( n= 9) using [ H)CGS 21680 as a radioligand probe. The maximum number of binding sites (B) (max) was 70% higher in patients with schizophrenia than in matched controls (609.4 +/- 259.1 354.0 +/- 156.4 fmol/mg protein, p=0.04). No significant difference could be discerned for the affinity of caffeine for adenosine A receptors between patients and controls. The increase in receptor density correlated with the dose of antipsychotic medication in chlorpromazine equivalents (r =0.61, = 0.014). We failed to provide evidence for a genetically determined reduction of adenosine A 2(A) receptors in schizophrenia. Instead, consistent with findings from animal experiments, our observation supports a role of adenosine A (2A) receptors in the molecular effects of antipsychotic drugs.
Deckert
Jürgen
J
Department of Psychiatry, University of Würzburg, Germany. deckertj@uni-muenster.de
Brenner
Markus
M
Durany
Nuria
N
Zöchling
Robert
R
Paulus
Werner
W
Ransmayr
Gerhard
G
Tatschner
Thomas
T
Danielczyk
Walter
W
Jellinger
Kurt
K
Riederer
Peter
P
D000241:Adenosine / Q000031:analogs & derivatives* / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D014150:Antipsychotic Agents / Q000627:therapeutic use; D002102:Cadaver; D002110:Caffeine / Q000378:metabolism; D035061:Control Groups; D003342:Corpus Striatum / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010627:Phenethylamines / Q000378:metabolism; D058906:Purinergic P1 Receptor Agonists; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism*; D015854:Up-Regulation
D014150:Antipsychotic Agents; D010627:Phenethylamines; D058906:Purinergic P1 Receptor Agonists; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D002110:Caffeine; D000241:Adenosine