Premium
D 1 Dopamine Receptors Can Interact with Both Stimulatory and Inhibitory Guanine Nucleotide Binding Proteins
Author(s) -
Sidhu Anita,
Sullivan Molly,
Kohout Trudy,
Balen Paul,
Fishman Peter H.
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.tb08312.x
Subject(s) - receptor , g protein , agonist , guanine , biochemistry , pertussis toxin , nucleotide , dopamine receptor , chemistry , biology , microbiology and biotechnology , gene
Pretreatment of striatal membranes with N ‐ethylmaleimide in the presence of a D 1 specific agonist inactivated endogenous guanine nucleotide binding proteins (G proteins), but not D, dopamine receptors, resulting in a loss of high‐affinity agonist binding sites. Such D 1 receptors were solubilized, mixed with exogenous G proteins from cells not containing D 1 receptors, and reconstituted into phospholipid vesicles. These reconstituted receptors were able to couple to the exogenous G proteins, and the proportion of agonist high‐affinity sites of the receptor (40–57%) was similar to levels obtained with naive receptors coupling to endogenous G proteins (40%) upon solubilization and reconstitution. These hybrid high‐affinity sites were fully modulated by guanine nucleotides. Pretreatment of cells with pertussis toxin prior to extraction of G proteins resulted in a 50% decrease in the proportion of high‐affinity sites; these sites remained sensitive to guanine nucleotides. When D, receptors were reconstituted with extracts of cyc − cells, which lack stimulatory G proteins, the proportion of high‐affinity sites was reduced to 31% of the total. Pertussis toxin treatment of the cyc − cells completely abolished the formation of high‐affinity sites. These results demonstrate that D 1 ‐dopaminergic receptors are able to couple to not only stimulatory G proteins (G s ), but also to inhibitory G proteins (G i ).