公開日 2019年10月28日
We show that cyclic guanosine monophosphate (cGMP)/cGMP-dependent protein kinase (PKG) pathway modulates nicotine- and clothianidin-induced currents. Indeed, increased cGMP affects the second part of the biphasic current voltage curve, corresponding to the nAChR2 receptors, while maintaining the guanosine triphosphate (GTP) level with GTP-γ-S increased nicotine currents through nAChR2.
We also demonstrated that inhibition of PKG activity with (8R,9S,11S)-(-)-9-methoxy-carbamyl-8-methyl-2,3,9,10-tetrahydro-8,11-epoxy-1H,8H,11H-2,7b,11a-trizadibenzo-(a,g)-cycloocta-(c,d,e)-trinden-1-one (KT5823), a PKG specific inhibitor, reduced nicotine-induced current amplitudes. KT5823 effect on nicotine currents is associated with calcium (Ca2+) activity because inhibition of Ca2+ concentration with cadmium chloride (CdCl2) abolished KT5823-induced inhibition mediated by nAChR2.
These results suggest that nicotine- and clothianidin-induced currents mediated by both α-bungarotoxin-insensitive nAChR1 and nAChR2 are coupled to the cAMP/PKA and cGMP/PKG pathways.
We also demonstrated that inhibition of PKG activity with (8R,9S,11S)-(-)-9-methoxy-carbamyl-8-methyl-2,3,9,10-tetrahydro-8,11-epoxy-1H,8H,11H-2,7b,11a-trizadibenzo-(a,g)-cycloocta-(c,d,e)-trinden-1-one (KT5823), a PKG specific inhibitor, reduced nicotine-induced current amplitudes. KT5823 effect on nicotine currents is associated with calcium (Ca2+) activity because inhibition of Ca2+ concentration with cadmium chloride (CdCl2) abolished KT5823-induced inhibition mediated by nAChR2.
These results suggest that nicotine- and clothianidin-induced currents mediated by both α-bungarotoxin-insensitive nAChR1 and nAChR2 are coupled to the cAMP/PKA and cGMP/PKG pathways.