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Mammalian olfactory receptors: pharmacology, G protein coupling and desensitization

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Abstract

The vertebrate olfactory system recognizes and discriminates between thousands of structurally diverse odorants. Detection of odorants in mammals is mediated by olfactory receptors (ORs), which comprise the largest superfamily of G protein-coupled receptors (GPCRs). Upon odorant binding, ORs couple to G proteins, resulting in an increase in intracellular cAMP levels and subsequent receptor signaling. In this review, we will discuss recently published studies outlining the molecular basis of odor discrimination, focusing on pharmacology, G protein activation, and desensitization of ORs. A greater understanding of the molecular mechanisms underlying OR activity may help in the discovery of agonists and antagonists of ORs, and of GPCRs with potential therapeutic applications.

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Abbreviations

AC:

Adenylyl cyclase

β1AR:

β1-Adrenergic receptor

β2AR:

β2-Adrenergic receptor

CaM:

Calmodulin

CaMKII:

Calcium/CaM-dependent protein kinase II

CNG channel:

Cyclic nucleotide-gated channel

GC:

Guanylyl cyclase

GG:

Grueneberg ganglion

GPCR:

G protein-coupled receptor

GRK:

GPCR kinase

Helix8:

Eighth intracellular helical domain

IC3:

Third intracellular loop

MOE:

Main olfactory epithelium

OB:

Olfactory bulb

OR:

Olfactory receptor

OSN:

Olfactory sensory neuron

PCR:

Polymerase chain reaction

PKA:

Protein kinase A

PKC:

Protein kinase C

PLC/IP3 :

Phospholipase C/inositol-1,4,5-triphosphate

SO:

Septal organ

TAAR:

Trace amine-associated receptor

TM:

Transmembrane

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Correspondence to Kazushige Touhara.

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Kato, A., Touhara, K. Mammalian olfactory receptors: pharmacology, G protein coupling and desensitization. Cell. Mol. Life Sci. 66, 3743–3753 (2009). https://doi.org/10.1007/s00018-009-0111-6

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  • DOI: https://doi.org/10.1007/s00018-009-0111-6

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