Competitive inhibition of [3H]spiperone binding to D-2 dopamine receptors in striatal homogenates by organic calcium channel antagonists and polyvalent cations.
The specific binding of [3H]spiperone (30 pM) to D-2 dopamine receptors in homogenates of the rat corpus striatum, as defined by the D-2 antagonist haloperidol (100 nM), was displaced by organic calcium channel antagonists and by polyvalent cations. Both classes of agents were able to totally displace [3H]spiperone binding by an apparently competitive mechanism in that the dissociation constant was increased while the density of binding sites was unchanged. The rank order of inhibition potency for the cations was Zn2+ greater than Cd2+ greater than La3+ greater than Cu2+ greater than Ni2+ greater than Co2+ greater than Mn2+ greater than Mg2+, Ca2+ greater than Ba2+. Of the organic calcium channel antagonists, D600 and verapamil were the most potent displacers of [3H]spiperone binding (IC50 values both 2.0 microM), while diltiazem possessed an IC50 of 33 microM. Nicardipine (IC50 6.0 microM) was the only 1,4-dihydropyridine to inhibit [3H]spiperone binding. The results suggest that sites labelled by [3H]spiperone also bind organic calcium channel antagonists and polyvalent cations.
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D002090:Butyrophenones / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002412:Cations / Q000494:pharmacology*; D003342:Corpus Striatum / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000378:metabolism*; D017448:Receptors, Dopamine D2; D013134:Spiperone / Q000378:metabolism*
D002090:Butyrophenones; D002121:Calcium Channel Blockers; D002412:Cations; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D013134:Spiperone