Specificity of metabotropic glutamate receptor 2 coupling to G proteins.
Amino Acid; Amino Acid Sequence; Animals; Calcium/metabolism; Electrophysiology; Gi-Go/metabolism; GTP-Binding Protein alpha Subunits; GTP-Binding Proteins/*metabolism; Metabotropic Glutamate/*metabolism; Molecular Sequence Data; Neurons/*drug effects/metabolism; Pertussis Toxin/*pharmacology; Rats; Receptors; Sequence Homology; Superior Cervical Ganglion/cytology; Wistar
Metabotropic glutamate receptor 2 (mGluR2) is a class 3 G protein-coupled receptor and an important mediator of synaptic activity in the central nervous system. Previous work demonstrated that mGluR2 couples to pertussis toxin (PTX)-sensitive G proteins. However, the specificity of mGluR2 coupling to individual members of the G(i/o) family is not known. Using heterologously expressed mGluR2 in rat sympathetic neurons from the superior cervical ganglion (SCG), the mGluR2/G protein coupling profile was characterized by reconstituting coupling in PTX-treated cells expressing PTX-insensitive mutant Galpha proteins and Gbetagamma. By employing this method, it was demonstrated that mGluR2 coupled strongly with Galphaob, Galphai1, Galphai2, and Galphai3, although coupling to Galphaoa was less efficient. In addition, mGluR2 did not seem to couple to the most divergent member of the G(i/o) family, Galphaz, although Galphaz coupled strongly to the endogenous alpha2 adrenergic receptor. To determine which Galpha proteins may be natively expressed in SCG neurons, the presence of mRNA for various Galpha proteins was tested using reverse transcription-polymerase chain reaction. Strong bands were detected for all members of the G(i/o) family (Galphao, Galphai1, Galphai2, Galphai3, Galphaz) as well as for Galpha11 and Galphas. A weak signal was detected for Galphaq and no Galpha15 mRNA was detected.
Kammermeier Paul J; Davis Margaret I; Ikeda Stephen R
Molecular pharmacology
2003
2003-01
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1124/mol.63.1.183" target="_blank" rel="noreferrer noopener">10.1124/mol.63.1.183</a>
Developmental pyrethroid exposure causes long-term decreases of neuronal sodium channel expression.
Animals; BDNF; Brain-Derived Neurotrophic Factor/metabolism; Cerebral Cortex/*drug effects/growth & development/metabolism; Corpus Striatum/*drug effects/growth & development/metabolism; Deltamethrin; Female; Inbred C57BL; Insecticides/*toxicity; Male; Messenger/metabolism; Mice; Neurodevelopmental; Neurons/*drug effects/metabolism; Nitriles/*toxicity; Pregnancy; Prenatal Exposure Delayed Effects/*metabolism; Pyrethrins/*toxicity; Pyrethroid; RNA; Sodium channel; Voltage-Gated Sodium Channels/*metabolism
Pyrethroid insecticide use has increased over recent years because of their low to moderate acute toxicity in mammals. However, there is increasing concern over the potential detrimental effects of pyrethroids on developing animals. Most recently, we have shown that developmental exposure to deltamethrin results in long-term neurobehavioral effects. Pyrethroids exert their toxicity by acting on the voltage-gated sodium channel (Nav), delaying channel inactivation and causing hyperexcitability in the nervous system. Previous in vitro studies found that exposure to agents that increase Na(+) influx, including deltamethrin decreased Nav mRNA expression. However, it is unknown whether this occurs in vivo. To determine whether developmental pyrethroid exposure decreases Nav mRNA expression, pregnant mice were exposed to the pyrethroid deltamethrin (0 or 3mg/kg) every three days throughout gestation and lactation. Nav mRNA expression was measured in the striatum and cortex of the offspring at 10-11 months of age, a time at which behavioral abnormalities were still observed. Developmental exposure to deltamethrin decreased expression of Nav mRNA in a region- and isoform-specific fashion by 24-50%. Deltamethrin exposure also resulted in the persistent down-regulation of brain-derived neurotrophic factor (Bdnf) in the striatum by 66% but not in the cortex, suggesting a plausible mechanism for some of the associated behavioral effects observed previously. Taken together these data suggest that developmental deltamethrin exposure results in persistent deficits in Nav and BDNF mRNA expression that may contribute to long-term behavioral deficits.
Magby Jason P; Richardson Jason R
Neurotoxicology
2017
2017-05
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.neuro.2016.04.002" target="_blank" rel="noreferrer noopener">10.1016/j.neuro.2016.04.002</a>