Olfactory receptor signaling.

The guanine nucleotide protein (G protein)-coupled receptors (GPCRs) superfamily represents the largest class of membrane protein in the human genome. More than a half of all GPCRs are dedicated to interact with odorants and are termed odorant-receptors (ORs). Linda Buck and Richard Axel, the Nobel Prize laureates in physiology or medicine in 2004, first cloned and characterized the gene family that encode ORs, establishing the foundations to the understanding of the molecular basis for odor recognition. In the last decades, a lot of progress has been done to unravel the functioning of the sense of smell. This chapter gives a general overview of the topic of olfactory receptor signaling and reviews recent advances in this field.

Physiological effect of olfactory stimuli inhalation in humans: an overview.

The importance of odorants in human life has long been recognized. Literature contains different approaches of physiological and psychological effects of odorant compounds, fragrances and essential oils. This work discusses odorants inhalation effect, based on an overview of major studies in humans. Beneficial effect of fragrances is mainly related to human behaviour. Studies document odorants influence in sympathetic and parasympathetic nervous systems, and neurophysiological brain activity. Moreover, odours compounds can act on the neuroendocrine system, neurotransmitters and neuromodulators, influencing psychological behaviour as well as body function. Odorant inhalation modulates physiological pathways, and in some cases, results in skin function regulation. The mechanism is incompletely elucidated. These findings suggest that olfactory system plays a role in central nervous system function beyond that of smell. In this overview, it was observed that odour compounds influenced stress biomarkers, dehydroepiandrosterone, oxidative stress, estradiol, dopamine, cutaneous barrier, sebum secretion and cutaneous immune system in humans. Some can be related with skin function. As the skin is associated with an extensive biochemical cascade and has complex mechanisms, studies have far to go, as there are processes not yet investigated related to skin that may be affected through olfaction. Future researches are needed to further understand and describe the mechanisms of action of physiological effects in fragrance compounds.

Structure of an odorant-binding protein from the mosquito Aedes aegypti suggests a binding pocket covered by a pH-sensitive "Lid".

BACKGROUND: The yellow fever mosquito, Aedes aegypti, is the primary vector for the viruses that cause yellow fever, mostly in tropical regions of Africa and in parts of South America, and human dengue, which infects 100 million people yearly in the tropics and subtropics. A better understanding of the structural biology of olfactory proteins may pave the way for the development of environmentally-friendly mosquito attractants and repellents, which may ultimately contribute to reduction of mosquito biting and disease transmission. METHODOLOGY: Previously, we isolated and cloned a major, female-enriched odorant-binding protein (OBP) from the yellow fever mosquito, AaegOBP1, which was later inadvertently renamed AaegOBP39. We prepared recombinant samples of AaegOBP1 by using an expression system that allows proper formation of disulfide bridges and generates functional OBPs, which are indistinguishable from native OBPs. We crystallized AaegOBP1 and determined its three-dimensional structure at 1.85 A resolution by molecular replacement based on the structure of the malaria mosquito OBP, AgamOBP1, the only mosquito OBP structure known to date. CONCLUSION: The structure of AaegOBP1 ( = AaegOBP39) shares the common fold of insect OBPs with six alpha-helices knitted by three disulfide bonds. A long molecule of polyethylene glycol (PEG) was built into the electron-density maps identified in a long tunnel formed by a crystallographic dimer of AaegOBP1. Circular dichroism analysis indicated that delipidated AaegOBP1 undergoes a pH-dependent conformational change, which may lead to release of odorant at low pH (as in the environment in the vicinity of odorant receptors). A C-terminal loop covers the binding cavity and this "lid" may be opened by disruption of an array of acid-labile hydrogen bonds thus explaining reduced or no binding affinity at low pH.

Functional expression of chemoreceptors with the help of a Guanine nucleotide exchange factor.

Odorant receptors and other chemoreceptors are usually poorly expressed in the plasma membrane of heterologous cells. A key point of regulation in G protein-mediated signaling is the interconversion between the active GTP-bound and inactive GDP-bound states of the Galpha subunit, which regulatory proteins, such as guanine nucleotide exchange factors (GEFs), can control. GEFs stimulate formation of the GTP-bound state of Galpha and therefore are considered to work as positive regulators of G protein-coupled receptor signaling. Ric-8B, a GEF that is specifically expressed in olfactory sensory neurons, promotes functional expression of odorant receptors in HEK293T cells because it amplifies the initially low receptor signaling through Galphaolf. This same strategy could be used to functionally express other types of chemoreceptors.

Inhibitory and excitatory effects of iodobenzene on the antennal benzoic acid receptor cells of the female silk moth Bombyx mori L.

As shown in single-sensillum recordings, iodobenzene has a bimodal effect on the receptor cell tuned to benzoic acid (BA) of the female silk moth Bombyx mori. Exposure to iodobenzene causes an inhibition of the response to BA. With stimulation by iodobenzene alone, a reduction of basic nerve impulse firing during exposure is followed by a transient post-stimulus excitation (rebound). We suggest that inhibition suppresses excitation during exposure but fades afterwards more rapidly than excitation. Due to the spatial equivalence of the iodine and the acid residue, these effects might indicate opposing interactions of iodobenzene with the specific site for the key compound BA. This is supported by the fact that substitutions by smaller halogens are less effective in both inhibition and rebound. The inhibitory effect but not the rebound with iodobenzene alone was also observed in receptor cells tuned to key compounds other than benzoic acid, e.g. in the cell most sensitive to 2,6-dimethyl-5-heptene-2-ol (DMH-cell) occurring in the same sensillum as the BA-cell, or in the bombykol- and bombykal-cells of the male. At least in these cells the inhibitory effect might reflect the action of iodobenzene on a general site, e.g. the lipid matrix of the plasma membrane of the receptor cells.

Chemical reception in vertebrate olfaction: evidence for multiple transduction pathways.

Odorant detection takes place at the receptor neurons of the olfactory epithelium and odorant discrimination relies in an important degree on these chemosensory cells. Here we review the evidence for the participation of multiple transduction pathways in the mechanisms of odor recognition in olfactory neurons.

Chemical reception in vertebrate olfaction: evidence for multiple transduction pathways

Odorant detection takes place at the receptor neurons of the olfactory epithelium and odorant discrimination relies in an important degree on these chemosensory cells. Here we review the evidence for the participation of multiple transduction pathways in the mechanisms of odor recognition in olfactory neurons

[Communication of gametes at distance. Chemotaxis and chemokinesis in spermatozoa in mammals]. / Comunicación de gametos a distancia. Quimiotaxis y quimiocinesis del espermatozoide en mamíferos.

The communication to distance is controlled chemically by the egg and the spermatozoa as part of the fertilization process, it has been studied intensily in invertebrate animals with outside fertilization. However studies with mammals offers a field of great interest. The chemoattractant from mammals spermatozoa include peptides or protein with a molecular weight of 1-20 KDa, hormones like progesterone, oxitocin, adrenalin and receptors on the spermatozoa head which are associated with the Guanylyl cyclase enzyme and G proteins, as well as other as like odorant receptor, rhodoopsin kinases and arresting. Chemotaxis allow us to understand the fertilization in human and also develop program for assisted reproduction. It is very important in the contraception.

Comunicación de gametos a distancia. Quimiotaxis y quimiocinesis del espermatozoide en mamíferos / At distance gamet communication. chemotaxis and chemokinesis of spermatozoo in mammals

La comunicación a distancia mediada químicamente entre el esperamatozoide o el óvulo como parte del proceso de fecundación a sido intensamente estudiado en especies de invertebrados con fecundación externa, sin embargo, su estudio en vertebrados, y especialmente mamíferos, abre un campo de gran interés. Los principales quimioatractantes en mamíferos que han sido encontrados incluyen a: péptidos de 1 a 20 KDa, proteínas, hormonas como progesterona, oxitocina, adrenalina y recientemente se han encontrado receptortes presentes en la cabeza del espermatozoide que están asociados a la enzima Guanilil ciclasa, vía proteína G, así como receptores de tipo olfatorio, rodopsina cinasa y arrestina. El estudio de la quimiotaxis permite además de entender algunos procesos de fecundación en gametos humanos y aplicarlos en los programas de reproducción asistida, puede ser de gran importancia en los programas de control prenatal