Selective activation of G-protein coupled receptors by volatile anesthetics.
Ion channels and ionotropic neurotransmitter receptors have long been investigated as the principle targets of inhaled volatile anesthetics (VAs), but emerging evidence suggests that G-protein coupled receptors (GPCRs) might also directly interact with VAs. To survey the extent of interaction between VAs and diverse GPCRs, we have turned to the 1000+ member family of olfactory receptors (ORs), taking advantage of their unique expression pattern of a single OR per neuron. Through optical imaging and electrophysiological recordings, we show that different VAs trigger the normal transduction cascade in distinct subsets of cells in a dose-dependant manner. Together with evidence of antagonism by odorants, this selective activation strongly implicates a direct action of VAs upon particular olfactory receptors. The finding that VAs stimulate nearly 8% of olfactory GPCRs suggests that probing related Class A GPCRs may reveal a pool of VA targets whose altered signaling contributes to anesthetic effects.
Peterlin
Zita
Z
Department of Biological Sciences, Columbia University, 920 Fairchild-MC#2439, 1212 Amsterdam Ave., New York, NY 10027, USA.
Ishizawa
Yumiko
Y
Araneda
Ricardo
R
Eckenhoff
Roderic
R
Firestein
Stuart
S
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006221:Halothane / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D000442:Octanols / Q000494:pharmacology; D009812:Odorants; D009831:Olfactory Mucosa / Q000187:drug effects* / Q000378:metabolism; D018034:Olfactory Receptor Neurons / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects* / Q000378:metabolism; D018035:Receptors, Odorant / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D012903:Smell / Q000187:drug effects / Q000502:physiology
D018685:Anesthetics, Inhalation; D000442:Octanols; D043562:Receptors, G-Protein-Coupled; D018035:Receptors, Odorant; D006221:Halothane