Binding of a novel dopaminergic agonist radioligand [3H]-fenoldopam (SKF 82526) to D-1 receptors in rat striatum.
Fenoldopam (SKF 82526), a dopamine agonist which exhibits D-1 receptor subtype selectivity, was evaluated as a radioligand for this receptor subtype. In saturation studies in rat striatal membrane preparations, [3H]-fenoldopam appeared to label a single binding site with a KD of 2.3 +/- 0.1 nM and a Bmax of 590 +/- 40 fmoles/mg protein. In competition binding experiments, binding was shown to be stereoselective, and rank ordering of affinities of dopaminergic and non-dopaminergic compounds closely correlated with potencies of these compounds in stimulating or inhibiting dopamine-sensitive adenylate cyclase (D-1) and in binding to D-1 sites labelled with the antagonist [3H]-cis-flupenthixol. The most potent competitors were the recently identified D-1 selective antagonists, SCH 23390 and SKF R-83566. [3H]-Fenoldopam was also used to assess agonist/D-1 receptor interactions. The results suggest that [3H]-fenoldopam is a useful and selective agonist radioligand for the D-1 receptor.
Flaim
K E
KE
Gessner
G W
GW
Crooke
S T
ST
Sarau
H M
HM
Weinstock
J
J
D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D001552:Benzazepines / Q000378:metabolism* / Q000494:pharmacology; D001667:Binding, Competitive; D002421:Caudate Nucleus / Q000378:metabolism*; D018818:Fenoldopam; D005475:Flupenthixol / Q000378:metabolism; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D011699:Putamen / Q000378:metabolism*; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000378:metabolism*; D017447:Receptors, Dopamine D1; D012964:Sodium / Q000494:pharmacology; D013134:Spiperone / Q000378:metabolism
D000067956:Adenylyl Cyclase Inhibitors; D001552:Benzazepines; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D006165:Guanylyl Imidodiphosphate; D013134:Spiperone; D012964:Sodium; D005475:Flupenthixol; D018818:Fenoldopam