Use of the exogenous Drosophila octopamine receptor gene to study Gq-coupled receptor-mediated responses in mammalian neurons.
Diverse excitatory and inhibitory neuronal responses are mediated via Gq-coupled receptors, but the lack of a systematic comparison of different receptors or neurons has hindered a better understanding of these responses. Such a comparison may be provided by an exogenous receptor that is activated by compounds that have no effect on endogenous receptors. We therefore expressed an invertebrate biogenic amine receptor, the Drosophila octopamine receptor, in rat cortical neurons and compared octopamine receptor-mediated responses with those mediated by the group I metabotropic glutamate receptor, the endogenous Gq-coupled receptor in rat cortical neurons. Stimulation of either receptor did not result in a calcium response in octopamine receptor-expressing neurons, although octopamine preferentially elicited a calcium increase in octopamine receptor-expressing PC12h cells, while enhancing the neuronal depolarization-induced calcium increase and the electrical excitability. The increased excitability was caused by inward currents resulting from a reduction in the leak current, which was voltage-independent and blocked by genistein, a non-selective tyrosine kinase inhibitor. These results show that, in cortical neurons, exogenous octopamine receptor in mushroom bodies activated the same cell signaling pathway as endogenous metabotropic glutamate receptor, suggesting that the diverse neuronal responses mediated by Gq-coupled receptors are due to the properties of different neurons, rather than to the properties of the receptors.
Morita
M
M
Laboratory of Cellular Neurobiology, School of Life Science, Tokyo University of Pharmacy and Life Science, 1432-1, Horinouchi, Hachioji, 192-0392, Japan. moritam@ls.toyaku.ac.jp
Susuki
J
J
Amino
H
H
Yoshiki
F
F
Moizumi
S
S
Kudo
Y
Y
D000200:Action Potentials / Q000187:drug effects / Q000235:genetics; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004330:Drosophila / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000187:drug effects / Q000235:genetics*; D018014:Gene Transfer Techniques; D008322:Mammals / Q000235:genetics*; D024521:Mushroom Bodies / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D016716:PC12 Cells; D018408:Patch-Clamp Techniques; D010716:Phosphatidylinositols / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects / Q000235:genetics*; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects / Q000378:metabolism; D017981:Receptors, Neurotransmitter / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics*; D009435:Synaptic Transmission / Q000187:drug effects / Q000235:genetics
D015220:Calcium Channels; D029721:Drosophila Proteins; D004791:Enzyme Inhibitors; C480734:OAMB protein, Drosophila; D010716:Phosphatidylinositols; D043562:Receptors, G-Protein-Coupled; D018094:Receptors, Metabotropic Glutamate; D017981:Receptors, Neurotransmitter; C104077:metabotropic glutamate receptor type 1; D011505:Protein-Tyrosine Kinases; D043802:GTP-Binding Protein alpha Subunits, Gq-G11