Halothane binding to a G protein coupled receptor in retinal membranes by photoaffinity labeling.
Article Details
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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
Drug Target Kind Organism Pharmacological Action Actions Halothane Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 Protein Humans UnknownOther/unknownDetails Halothane Neuropeptide S receptor Protein Humans UnknownOther/unknownDetails Halothane Rhodopsin Protein Humans UnknownOtherDetails