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Human Olfactory receptors: their role in odor perception and as new targets for
diagnosis and therapy
Hanns Hatt Dept. Cellphysiol. Ruhr-University Bochum
Scents indicate things, make promises, attract attention and stimulate imagination,
feed anxieties and hopes: they are the salt in the atmospheric soup. We regard
seeing and hearing as more important sensory functions, because they contribute
more to conscious, cognitive processes of perception - but at moments of the
greatest enjoyment we close our eyes and taste the scent, smell the taste. Before the
spirit and beauty of a person can fascinate us, our nose must become infatuated.
The olfactory system in the nose acts as a window, monitoring environmental
chemical information and convert chemical stimuli in electrical nerve impulses which
are conducted along the olfactory sensory neuron to their glomerular target in the
brain. Olfactory receptors (ORs) activation shows the distinguished (cAMP-based)
transduction pathway for odorant perception. In 1991 Buck and Axel discovered the
olfactory gene family, the largest gene family in the human genome, and postulated
an exclusive expression in the olfactory epithelium. However, recent whole genome
sequencing data from our and other labs show that ORs have been found in every
tissue of human body which was analyzed by next generation sequencing. The
importance of such ectopic expression of ORs is raised since the physiological
function of some of ORs was characterized. When identifying additional expression
profiles and functions of OR in non-olfactory tissue, there are limitations posed by the
deorphanization of ORs concerning the activated ligands and by the small number of
antibodies available. In contrast to the olfactory sensory neurons which are believed
to express all 350 functional OR genes (only one OR type per cell), cells in nonolfactory tissues tend to express more than one individual OR gene per cell. In
addition, some of the signaling pathways in non-olfactory tissues seem to involve
completely different components in comparison to the olfactory neurons.
What is the functional role of these ectopically expressed olfactory receptors?
Evidences rapidly accumulate that ORs participate in important cellular processes
outside its primary sensorial organ where they function in odor detection and
discrimination. In our lab the functional expression of the first was demonstrated in
spermatozoa (2004). In the meantime we could show the existence and function of
ORs in the cardiovascular system (heart, blood cells), the gastrointestinal system
(small intestine, liver, pancreas), the genito-urinary system (kidney, testis,
spermatozoa, prostate), the respiratory system (lung, smooth muscle cells), the skin
(keratinocytes, melanocytes) and sensory organs (retina). Interestingly we found a
broad spectrum of important functions like cell-cell communication and recognition,
tissue injury, repair and regeneration, cancer growth, progression and metastasis,
nutrient sensing and muscle contraction. Nevertheless the functional importance of
ectopic ORs is still not sufficiently understood. Studies seeking to determine the
function of ectopic ORs are still in its infancy and require further intensive exploration.
However, the potential of ORs to serve a target for a wide range of clinical
approaches is indeed given. This hold promises that the knowledge gained by future
investigations would lead to deepen our understanding of OR function in health and
disease and may provide the basis for the development of applications in diagnosis
and therapies in near future.