Voltage-sensitivity at the human dopamine D2S receptor is agonist-specific.
Recently, we and others have shown that agonist potencies at some, but not all, G protein-coupled receptors are voltage-sensitive. Several of those studies employed electrophysiology assays in Xenopus oocytes with G protein-coupled potassium channels as a readout. Using this assay, we have now obtained evidence that voltage-sensitivity at the dopamine D(2S) receptor is agonist-specific. Whereas the potency of dopamine at the D(2S) receptor is decreased by depolarization, the potencies of beta-phenethylamine, p- and m-tyramine are voltage-insensitive. Furthermore, both monohydroxylated and non-hydroxylated N,N-dipropyl-2-aminotetralin compounds are voltage-sensitive. Differential activation of G protein subtypes or differential ratios between effector and active G protein do not underlie this agonist-selective voltage-sensitivity. This is the first demonstration of voltage-sensitive and voltage-insensitive behaviour of different agonists acting via the same receptor.
Sahlholm
Kristoffer
K
Department of Neuroscience, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Marcellino
Daniel
D
Nilsson
Johanna
J
Fuxe
Kjell
K
Arhem
Peter
P
D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D055724:Electrophysiological Phenomena; D005260:Female; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D009865:Oocytes; D010627:Phenethylamines / Q000494:pharmacology; D017448:Receptors, Dopamine D2 / Q000819:agonists* / Q000502:physiology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D014439:Tyramine / Q000494:pharmacology; D014981:Xenopus
D010627:Phenethylamines; D017448:Receptors, Dopamine D2; D013764:Tetrahydronaphthalenes; C113776:dopamine D2L receptor; C016891:N,N-dipropyl-2-aminotetralin; C029261:phenethylamine; D014439:Tyramine