Selective labelling of dopamine (D2) receptors in rat striatum by [3H]domperidone but not by [3H]spiperone.
Specific binding of [3H]spiperone and [3H]domperidone, displaceable by 1 microM d-butaclamol, was examined in rat striatal membranes. Initial saturation and displacement experiments indicated that [3H]spiperone bound to more sites than [3H]domperidone and that, whilst all displacing drugs were more potent against [3H]domperidone, this difference in potency was greatest for dopamine agonists and specific antagonists and least for 5HT-related drugs. Sulpiride displaced [3H]spiperone biphasically, and was used at a concentration of 50 microM to examine two classes of [3H]spiperone binding: site 1 displaceable by sulpiride, and site 2 displaceable by butaclamol but not by sulpiride. Site 1 had twice the capacity of site 2 and ten times the affinity for [3H]spiperone. Dopaminergic drugs displaced preferentially from site 1, whilst 5HT-related drugs were more potent against site 2. GTP reduced the potency of dopamine, noradrenaline and, to a lesser extent, 5HT at site 1, but had no effect at site 2. [3H]Domperidone sites had the same capacity as [3H]spiperone site 1, and dopamine, noradrenaline and 5HT, in the absence or presence of GTP, and sulpiride had essentially identical affinities for [3H]domperidone sites and [3H]spiperone site 1. It is concluded that [3H]domperidone and [3H]spiperone label an identical population of dopamine (D2) receptors, whilst [3H]spiperone also labels a substantial number of non-dopamine sites, at least some of which are 5HT-related. [3H]spiperone also labels a substantial number of non-dopamine sites, at least some of which are 5HT-related. [3H]Domperidone is the better radioligand for dopamine receptors.
D000818:Animals; D001665:Binding Sites; D002090:Butyrophenones / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism*; D004294:Domperidone / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000378:metabolism*; D012701:Serotonin / Q000494:pharmacology; D013134:Spiperone / Q000378:metabolism*; D013469:Sulpiride / Q000494:pharmacology; D014316:Tritium
D002090:Butyrophenones; D011954:Receptors, Dopamine; D014316:Tritium; D012701:Serotonin; D013134:Spiperone; D004294:Domperidone; D013469:Sulpiride; D006160:Guanosine Triphosphate