Autoradiography of P2x ATP receptors in the rat brain.
1. Binding of a P2x receptor specific radioligand, [3H]-alpha,beta-methylene adenosine triphosphate ([3H]-alpha,beta-MeATP) to sections of rat brain was reversible and association/dissociation parameters indicated that it consisted of two saturable components. Non-specific binding was very low (< 7% at 10 nM ligand concentration). 2. The binding was completely inhibited by suramin (IC50 approximately 14-26 microM) but none of the ligands specific for P2y receptors such as 2-methylthio-adenosine triphosphate (2-methyl-S-ATP) and 2-chloro-adenosine triphosphate (2-C1-ATP) nor 2-methylthio-adenosine diphosphate (2-methyl-S-ADP) a ligand for the P2 receptor on blood platelets ('P2T' type) produced strong inhibitions except for P1,P4-di(adenosine-5')tetraphosphate (Ap4A). 3. Inhibitors of Na+,K(+)-dependent adenosine triphosphatase (ATPase) ouabain, P1-ligand adenosine and an inhibitor of transport of, respectively, adenosine and cyclic nucleotides, dilazep, had no effect. 4. The highest density of P2x binding sites was found to be in the cerebellar cortex but the binding sites were present in all major brain regions, especially in areas known to receive strong excitatory innervation.
Balcar
V J
VJ
Department of Anatomy and Histology, University of Sydney, Australia.
Li
Y
Y
Killinger
S
S
Bennett
M R
MR
D000244:Adenosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D001667:Binding, Competitive / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D001933:Brain Stem / Q000187:drug effects / Q000378:metabolism; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004109:Dilazep / Q000494:pharmacology; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008024:Ligands; D008297:Male; D010042:Ouabain / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013498:Suramin / Q000494:pharmacology; D013788:Thalamus / Q000187:drug effects / Q000378:metabolism; D013873:Thionucleotides / Q000494:pharmacology
D008024:Ligands; D018048:Receptors, Purinergic P2; D013873:Thionucleotides; C002480:methylthio-ADP; C006979:2-chloro-ATP; D010042:Ouabain; D013498:Suramin; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D004109:Dilazep; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; C008501:2-methylthio-ATP