Modulation of dopamine D3 receptor binding by N-ethylmaleimide and neurotensin.
GTP or G protein inactivation by N-ethylmaleimide reduced the Bmax value but not the KD value of 7-[3H]hydroxy-N,N-di-n-propyl-2-aminotetralin ([3H]7-OH-DPAT) binding in the rat subcortical limbic area. Neurotensin (10 nM) increased the KD and the Bmax values of [3H]7-OH-DPAT binding, and these effects persisted also following N-ethylmaleimide pretreatment. N-Propylnorapomorphine, quinpirole, raclopride, and remoxipride inhibited [3H]7-OH-DPAT binding with Ki values of 0.093, 1.97, 10.6, and 710 nM, respectively. These findings indicate that the D3 receptor is coupled to G proteins in the brain, and that neurotensin can modulate D3 agonist binding by a G protein-independent mechanism.
Liu
Y
Y
Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Hillefors-Berglund
M
M
von Euler
G
G
D000818:Animals; D001667:Binding, Competitive; D002462:Cell Membrane / Q000378:metabolism; D015259:Dopamine Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005033:Ethylmaleimide / Q000494:pharmacology*; D007700:Kinetics; D008032:Limbic System / Q000378:metabolism*; D008297:Male; D009496:Neurotensin / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013764:Tetrahydronaphthalenes / Q000378:metabolism
D015259:Dopamine Agents; C493595:Drd3 protein, rat; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013764:Tetrahydronaphthalenes; D009496:Neurotensin; D005033:Ethylmaleimide; C031349:7-hydroxy-2-N,N-dipropylaminotetralin