Premium
Affinity Shifts Induced by Cations Do Not Reliably Predict the Agonistic or Antagonistic Nature of Ligands at Brain Dopamine Receptors
Author(s) -
Urwyler Stephan
Publication year - 1987
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1987.tb01008.x
Subject(s) - affinities , receptor , chemistry , dopamine , dopamine receptor d2 , dopamine receptor , agonistic behaviour , dopamine receptor d1 , stereochemistry , biophysics , biochemistry , neuroscience , biology , psychology , psychiatry , aggression
The effects of Ca 2+ 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°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‐tetrahy‐dronaphthalene were clearly lower than at room tempera‐re. 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 Ca 2+ 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 Ca 2+ ions, this mechanism might play a role in the regulation of receptor affinities in synaptic transmission, in addition to that exerted by guanyl nucleotides.