Cloning, functional expression and characterization of a human olfactory receptor.
The human olfactory system can recognize and discriminate a large number of different odorant molecules. The detection of chemically distinct odorants begins with the binding of an odorant ligand to a specific receptor protein on the olfactory neuron cell surface. To address the problem of olfactory perception at a molecular level, we have cloned, functionally expressed and characterized the first human olfactory receptor (OR 17-40). Application of a mixture of hundred different odorants elicited a transient increase in intracellular calcium at HEK 293-cells which were transfected with a plasmid containing the receptor encoding DNA and a membrane import sequence. By subdividing the odorant mixture in smaller groups we could identify a single component which represented the only effective substance: helional. Testing some structurally closely related molecules we found only one other compound which also could activate the receptor: heliotropyl acetone. All other compounds tested were completely ineffective. These findings represent the beginning of molecular understanding of odorant recognition in humans.
Hatt
H
H
Ruhr University Bochum, Dept. Cell Physiology, Germany. hatt@cphys.ruhr-uni-bochum.de
Gisselmann
G
G
Wetzel
C H
CH
D001547:Benzaldehydes / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D052117:Benzodioxoles; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D003001:Cloning, Molecular; D004963:Estrenes / Q000494:pharmacology; D006801:Humans; D008969:Molecular Sequence Data; D009812:Odorants; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D018035:Receptors, Odorant / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012451:Safrole / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D014162:Transfection
D001547:Benzaldehydes; D052117:Benzodioxoles; D004963:Estrenes; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; D018035:Receptors, Odorant; D011994:Recombinant Proteins; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; C100058:vanillin; C005454:piperonal; D012451:Safrole; D002118:Calcium