New detection of brain dopamine receptors with (3H)dihydroergocryptine.
Because dihydroergocryptine (DHE) and closely related ergots are dopamine-mimetic agonists, we tested [3H]DHE as a possible ligand for [3H]dopamine receptors in the calf caudate. In order to avoid [3H]DHE from tagging alpha-adrenergic receptors, an excess of 500 nM phentolamine was used to block these sites, permitting the dopamine receptors to be measured separately. Specific binding of [3H]DHE was defined as total binding minus that occurring in the presence of 1 muM (+)-butaclamol. Excess phentolamine reduced the specific binding of [3H]DHE from 328 down to 138 fmol/mg, the difference presumably representing alpha-receptors. The KD for [3H]DHE was 0.55 nM (with or without phentolamine), and this high affinity site was blocked (in the presence of phentolamine) by 250nM apomorphine, 650 nM dopamine, and 1200 mM (minus)-norepinephrine, indicating that[3H]DHE was binding to dopamine receptors. All neuroleptics blocked specific [3H]DHE binding in direct relation to the clinical potency of the neuroleptic. The displacement of specific [3H]DHE binding by dopamine or by norepinephrine (in the presence of phentolamine) revealed two subsets of dopamine receptors.
D000818:Animals; D001667:Binding, Competitive; D002417:Cattle; D002421:Caudate Nucleus / Q000378:metabolism*; D004088:Dihydroergotoxine / Q000378:metabolism*; D007700:Kinetics; D010646:Phentolamine / Q000494:pharmacology; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D014149:Tranquilizing Agents / Q000494:pharmacology
D011954:Receptors, Dopamine; D014149:Tranquilizing Agents; D004088:Dihydroergotoxine; D010646:Phentolamine