TY - JOUR
T1 - Agonist‐Selective Protection of the Opioid Receptor‐Coupled G Proteins from Inactivation by 5′‐p‐fluorosulphonylbenzoyl Guanosine
AU - Wong, Y. H.
AU - Demoliou‐Mason, C. D.
AU - Hanley, M. R.
AU - Barnard, E. A.
PY - 1990
Y1 - 1990
N2 - Abstract: 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[8‐3H]guanosine 5′‐triphosphate binding sites. Using 1 mM 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 Gi or Go, proteins associated with opioid receptors.
AB - Abstract: 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[8‐3H]guanosine 5′‐triphosphate binding sites. Using 1 mM 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 Gi or Go, proteins associated with opioid receptors.
KW - 5′‐p‐fluorosulphonylbenzoyl guanosine
KW - GTP‐binding proteins
KW - Opioid receptors
UR - http://www.scopus.com/inward/record.url?scp=0025008814&partnerID=8YFLogxK
U2 - 10.1111/j.1471-4159.1990.tb13280.x
DO - 10.1111/j.1471-4159.1990.tb13280.x
M3 - Article
C2 - 2152798
AN - SCOPUS:0025008814
SN - 0022-3042
VL - 54
SP - 39
EP - 45
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
IS - 1
ER -