Link between dopamine D1 and D2 receptors in rat and human striatal tissues.
Many psychomotor behaviors depend on an interaction between dopamine D(1) and D(2) receptors. This study tested the hypothesis that agonist stimulation of dopamine D(1) receptors leads to the conversion of D(2) receptors from a state of high affinity for dopamine into a state of low affinity for dopamine. To test this hypothesis, dopamine was competed against [(3)H]raclopride for binding to rat and human striatal homogenates. Although the detection of high-affinity states of the dopamine D(2) receptor in rat or postmortem human striatum is normally difficult because the proportions of such sites are very low in the presence of physiological concentrations of sodium ions, the present work found that in the presence of 100 nM SCH 23390 to block D(1) receptors, a significant proportion of D(2) high-affinity sites were unmasked and readily revealed to be 10-35% of the D(2) population, illustrating the presence of a strong D(1)-D(2) link in both rat and human striata.
Seeman
Philip
P
Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada M5S 1A8. philip.seeman@utoronto.ca
Tallerico
Teresa
T
D000328:Adult; D000368:Aged; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D001667:Binding, Competitive; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000378:metabolism / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D005260:Female; D006801:Humans; D008297:Male; D020891:Raclopride / Q000494:pharmacology; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism*; D012559:Schizophrenia / Q000378:metabolism
D001552:Benzazepines; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D020891:Raclopride; D004298:Dopamine