Evidence for Different States of the Dopamine Dl Receptor: Clozapine and Fluperlapine May Preferentially Label an Adenylate Cyclase‐Coupled State of the Dl Receptor

摘要: : It has been shown previously that typical neuroleptics have higher affinities for 3,4-dihydroxyphenyl-ethylamine (dopamine) Dl receptors as labeled by(R)- (+)- 8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1 -N-3-benzazepine-7-ol ([3H]SCH 23390) than inhibiting dopamine-stimulated adenylate cyclase. We now report the atypical neuroleptics, clozapine and fluperlapine, exhibit characteristics opposite to i.e., they affinity cyclase [3H]SCH 23390 binding. A variety of compounds, clozapine, dopamine, were tested their capacity affect rate constants binding; these experiments revealed no effect any compound on on-rate or off-rate Treatment striatal membranes with phospholipase A2 (PLA2) caused a rapid decrease in Bmax value binding Kd value. The cyclase, both unstimulated, dopamine-, fluoride-, forskolin-stimulated activity, was far less sensitive PLA2. filipine (NH4SO4 produced, did PLA2 treatment, decline However, agents stimulated In conclusion, comparison pharmacological suggests existence two different sites. exclude possibility allosterically coupled Instead our results favor receptor exists states/conformations, cyclase-coupled uncoupled, further, fluperlapine may dopamine target.