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Neurotensin Decreases the Affinity of Dopamine D 2 Agonist Binding by a G Protein‐Independent Mechanism
Author(s) -
Euler Gabriel,
Ploeg Ingeborg,
Fredholm Bertil B.,
Fuxe Kjell
Publication year - 1991
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.1471-4159.1991.tb02578.x
Subject(s) - neurotensin , pertussis toxin , agonist , g protein , chemistry , dithiothreitol , gtp' , medicine , raclopride , endocrinology , binding site , receptor , antagonist , biochemistry , biology , neuropeptide , enzyme
To examine whether GTP‐binding proteins (G proteins) mediate the ability of neurotensin to lower the affinity of dopamine D 2 agonist binding, the modulation by neurotensin in vitro of N ‐[ 3 H]propylnorapotnorphine ([ 3 H]NPA) binding was investigated following pretreatment with pertussis toxin and N ‐ethylmaleimide in rat neostriatal membranes. Preincubation with N ‐ethylmaleimide (100 μ M ) markedly inhibited pertussis toxin‐induced back‐ADP ribosylation of three proteins with apparent molecular masses of 41, 40, and 39 kDa, respectively. This inhibition was prevented by adding dithiothreitol (250 μ M ) during the preincubation. N ‐Ethylmaleimide increased the K D (180 ± 30%) and decreased the B max (−31 ± 9%) of [ 3 H]NPA binding sites but did not affect the binding properties of the selective D 2 antagonist [ 3 H]raclopride. N ‐Ethylmaleimide pretreatment did not affect the neurotensin (3 n M )‐induced increase in the K D of [ 3 H]NPA binding sites. Pertussin toxin treatment in vivo and in vitro was similarly ineffective. In conclusion, the present study indicates that neurotensin modulation of D 2 agonist binding in neostriatal membranes is not mediated by G proteins.