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Agonist‐Selective Protection of the Opioid Receptor‐Coupled G Proteins from Inactivation by 5′‐ p ‐fluorosulphonylbenzoyl Guanosine
Author(s) -
Wong Y. H.,
DemoliouMason C. D.,
Hanley M. R.,
Barnard E. A.
Publication year - 1990
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.1471-4159.1990.tb13280.x
Subject(s) - agonist , chemistry , guanosine , neurotensin , gtpgammas , g protein , receptor , guanine , biochemistry , competitive antagonist , opioid , pharmacology , nucleotide , biology , neuropeptide , gene
The guanine nucleotide analogue, 5′‐ p ‐fluorosul‐phonylbenzoyl guanosine (FSBG), can react covalently with GTP‐binding proteins (G proteins). In rat brain membranes, FSBG causes a time‐dependent loss of β,γ‐imido[8‐ 3 H]guanosine 5′‐triphosphate binding sites. Using 1 m M FSBG, the guanyl nucleotide modulation of opioid agonist binding is abolished, whereas the guanyl nucleotide sensitivity of neurotensin binding is retained. The action of FSBG can be prevented by the presence of opioid agonists, but not the antagonist naloxone. Iodoacetamide treatment of membranes in the presence of agonist, but not antagonist, can attenuate the action of FSBG in blocking guanyl nucleotide modulation of opioid agonist binding. These results suggest that FSBG covalently modifies essential thiol groups, whose exposure to the reagent is modified by agonist occupancy of the receptor, on a species of G protein linked to opioid receptors, but not on a species of G protein linked to neurotensin receptors. Thus, FSBG may have selectivity for the forms of G i or G o , proteins associated with opioid receptors.