Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Saito, S. et al.

Halothane facilitates the translocation of GRK-2 and phosphorylation of beta2-adrenergic receptor in rat synaptosomes.

PURPOSE: To examine the effect of halothane on beta2-adrenergic receptor phosphorylation and on G-protein coupled receptor kinase (GRK), responsible for beta2-receptor downregulation. METHODS: Rat forebrain synaptosomes were incubated for 30 min with halothane 1 or 2%. The cytosolic and membrane fractions were separated, and phosphorylation activity of recombinant beta2-adrenergic receptor was quantified autoradiographically using 32P labeled adenosine triphosphate. Phosphorylation activity of a specific GRK-2 substrate, was examined by measuring 32P binding. Subcellular localization of the enzyme was immunologically analyzed by Western blotting. RESULTS: Halothane 2% decreased the phosphorylation activity of the recombinant receptor in the cytosol fraction, regardless of 10 microM isoproterenol (ISP) (P<0.01), which activity in the membrane fraction was increased (P<0.01). Phosphorylation activity of the synthetic peptide decreased in the cytosol obtained from synaptosomes exposed to halothane 2% (P<0.05). In contrast, activity in the membrane increased by exposure to halothane 2% (P<0.01). The concentration of GRK-2 decreased in the cytosol obtained from synaptosomes exposed to halothane 1% or 2% (decreases of 8.3+/-1.2% @ 1%, and 18.0+/-2.1% @ 2%, P<0.05). In the membrane, exposure to halothane 1% or 2% increased the GRK-2 amount dose dependently (22.5+/-3.1% @ 1%, and by 45.7+/-6.1% @ 2%, P<0.01). CONCLUSION: Halothane could facilitate translocation of GRK-2 and possibly promote the downregulation of beta2-adrenergic receptors in the synaptic membrane. The anesthetic action and hemodynamic suppressive action of halothane may be related to this phenomenon.[1]

References

Halothane facilitates the translocation of GRK-2 and phosphorylation of beta2-adrenergic receptor in rat synaptosomes. Saito, S., Kadoi, Y., Ohyama, A., Goto, F. Canadian journal of anaesthesia = Journal canadien d'anesthésie. (2000) [Pubmed]

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