Halothane binding to a G protein coupled receptor in retinal membranes by photoaffinity labeling.

Article Details

Citation

Ishizawa Y, Sharp R, Liebman PA, Eckenhoff RG

Halothane binding to a G protein coupled receptor in retinal membranes by photoaffinity labeling.

Biochemistry. 2000 Jul 25;39(29):8497-502.

PubMed ID
10913255 [ View in PubMed
]
Abstract

General anesthetics have been reported to alter the functions of G protein coupled receptor (GPCR) signaling systems. To determine whether these effects might be mediated by direct binding interactions with the GPCR or its associated G protein, we studied the binding character of halothane on mammalian rhodopsin, structurally the best understood GPCR, by using direct photoaffinity labeling with [(14)C]halothane. In the bleached bovine rod disk membranes (RDM), opsin and membrane lipids were dominantly photolabeled with [(14)C]halothane, but none of the three G protein subunits were labeled. In opsin itself, halothane labeling was inhibited by unlabeled halothane with an IC(50) of 0.9 mM and a Hill coefficient of -0.8. The stoichiometry was 1.1:1.0 (halothane:opsin molar ratio). The IC(50) values of isoflurane and 1-chloro-1,2, 2-trifluorocyclobutane were 5.0 and 15 mM, respectively. Ethanol had no effect on opsin labeling by halothane. A nonimmobilizer, 1, 2-dichlorohexafluorocyclobutane, inhibited halothane labeling by 50% at 0.05 mM. The present results demonstrate that halothane binds specifically and selectively to GPCRs in the RDM. The absence of halothane binding to any of the G protein subunits strongly suggests that the functional effects of halothane on GPCR signaling systems are mediated by direct interactions with receptor proteins.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
HalothaneGuanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2ProteinHumans
Unknown
Other/unknown
Details
HalothaneNeuropeptide S receptorProteinHumans
Unknown
Other/unknown
Details
HalothaneRhodopsinProteinHumans
Unknown
Other
Details