Effects of organophosphorus insecticides on G-protein coupled receptor kinase 2-mediated phosphorylation of m2 muscarinic receptors

  Objective   To explore the effectof organophosphorus insecticides(OPs)on G-protein coupled receptor kinase 2-mediated phosphorylation of m2 muscarinic receptors in vitro and to understand alternative target of the OPs for human and other animals.

  Methods   Invitro experiments, purified m2 receptor was incubated with varying concentration of paraoxon, chlorpy rifos oxon or the parentinsecticides along with G-protein coupled receptor kinase 2(GRK 2)andC-P32 ATP.Proteins were separated byelectrophoresis and autoradiog rams developed.

  Results   Chlor pyrifos ox on inhibited phosphor ylation of m2 muscarinic receptors by GRK 2 with a median inhibition concentration(IC₅₀)of approximately 70 μmol/L.Chlorpyrifos also inhibited m2 receptors phosphorylation, butwas less potentand less efficacious than thatof chlo rpyrifos oxon.Interestingly, paraox on and parathion had little effecton the receptor phosphory lation under the same conditions.

  Conclusion   Chlorpyrifos ox on and chlorpy rifos may therefore alter GRK 2-mediated regulatory pathways for m2 receptors by directinteraction with m2 recptor.These differential actions could contribute to differences in toxicity follow ing exposure to differentorg anophosphorus toxicants.