Affinity shifts induced by cations do not reliably predict the agonistic or antagonistic nature of ligands at brain dopamine receptors.
The effects of Ca2+ and Na+ ions on the affinities of rat striatal dopamine D1 and D2 receptors for a wide range of agonists and antagonists were investigated. These experiments were performed at 37 degrees C, since it was found that at this physiological temperature D2 receptor affinities for dopamine and 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene were clearly lower than at room temperature. No correlation was found between the effects of the cations on the affinities of compounds for D1 and D2 receptors and their agonistic or antagonistic nature. On the other hand, the Hill coefficients of agonists but not of antagonists were consistently and significantly below unity, with either Ca2+ or Na+ ions present and at both receptors. This suggests the existence of yet another type of heterogeneity of D1 and D2 receptor forms, to which agonists but not antagonists are sensitive. It is thus concluded that changes in D1 and D2 receptor affinities induced by cations do not predict the agonistic or antagonistic nature of a compound. However, since dopamine itself was sensitive to Na+ or Ca2+ ions, this mechanism might play a role in the regulation of receptor affinities in synaptic transmission, in addition to that exerted by guanyl nucleotides.
D000818:Animals; D001552:Benzazepines / Q000378:metabolism; D002118:Calcium / Q000494:pharmacology*; D002412:Cations; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D018492:Dopamine Antagonists; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D012964:Sodium / Q000494:pharmacology*; D013134:Spiperone / Q000378:metabolism; D013696:Temperature; D013764:Tetrahydronaphthalenes / Q000378:metabolism; D014316:Tritium
D001552:Benzazepines; D002412:Cations; D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013764:Tetrahydronaphthalenes; D014316:Tritium; D013134:Spiperone; C011639:ADTN; D012964:Sodium; D002118:Calcium; D004298:Dopamine