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Quantal-like current fluctuations induced by odorants in olfactory receptor cells.

Many sensory systems have evolved signal detection capabilities that are limited only by the physical attributes of the stimulus. For example, 'hair' cells of the inner ear can detect displacements of atomic dimensions. Likewise, both in vertebrates and in invertebrates photoreceptors can detect a single photon. The olfactory stimulus also has a quantal unit, the single odorant molecule. Insects are reportedly able to detect a single pheromone molecule, whereas quantal responses in vertebrate olfactory receptor cells have not been reported yet. Psychophysical measurements indicate that a minimum of 50 odorant molecules are necessary for human olfactory detection, suggesting that an individual receptor may be activated by a single odorant molecule. We report here measurements of current fluctuations induced by odorants that suggest a quantal event of about 0.3-1 pA, presumably triggered by the binding of a single odorant molecule.

Ambystoma↗

Achyrocline satureioides essential oils from southern Brazil and Uruguay.

The essential oils of the aerial parts of Achyrocline satureioides (D.C.) Lam., a regional medicinal plant, from different collection locations in the South of Brazil and Uruguay were examined by GC and GC-MS. Monoterpene and sesquiterpene hydrocarbons were the main fractions of both the oils from Brazil and Uruguay. The oxygenated monoterpenes and sequiterpenes were at much lower percentage in both samples. The Uruguayan samples have 1,8-cineole which is not present in the Brazilian samples and has not been reported in other samples from Brazil. The results indicated a high biodiversity of the native populations of A. satureioides.

Asteraceae↗

Different stereoselectivity in the reduction of pulegone by Mentha species.

Aqueous solutions of [2H]-labeled pulegone enantiomers were fed to Mentha spicata ssp. spicata L. and Mentha spicata ssp. crispata L. shoot tip and first leaf pair. After solid phase microextraction the essential oil was analysed with enantioselective multidimensional gas chromatography/mass spectrometry. Both Mentha spicata species were able to convert labelled (1R)- and (1S)-pulegone at the same rate into the corresponding menthone and isomenthone, indicating an unspecific process. The reduction of both pulegone enantiomers preferably led to the cis-stereoisomers. The observed stereoselectivity is completely different from those of pulegone reduction by Mentha x piperita L.

Cyclohexane Monoterpenes↗

[Effect of the phytogenic secretolytic drug Gelomyrtol forte on mucociliary clearance of the maxillary sinus].

BACKGROUND: To date, there has not been sufficient experimental evidence to demonstrate the pharmacological effect of secretolytic and mucolytic drugs. METHODS: Scintigraphic studies to detect the mucociliary clearance in the maxillary sinus before and after application of the secretolytic drug Gelomyrtol forte were performed on four healthy persons and one patient after sinus surgery. The most important parameter was the mucociliary transport velocity of the "region of interest-maxillary sinus" and the increase of radioactivity accumulated in a tampon placed in the middle meatus of the nose. Measurements were done with a gamma-camera, 99 m Technetium-sulphurcolloid was used as the radiopharmacentical. A dose of 1 MBq in 0.2 ml NaCl-solution was injected into the maxillary sinus. RESULTS: The results show a clear increase of mucociliary transport velocity in the maxillary sinus after intake of secretolytics in connection with an increase of radioactivity in the tampon. DISCUSSION: The results can be explained by the secretolytic and secretomotoric effects of the investigated drug. CONCLUSION: The study reveals that ethereal oils have secretolytic effects and also have a pharmacological effect on the mucociliary apparatus.

Adult↗

Temporal competition between odorants: effect of different time intervals on the perception of monorhinic and dichorhinic binary mixtures.

Backward masking and its possible connection with the perception of odour mixtures has been investigated. Temporal competition between odorants in a binary mixture was tested by artificially creating a delay between one odour (the target) and a second, stronger, odour (the mask) during a single natural sniff. To test the influence of central versus peripheral competition, the same mixture was presented either monorhinically or dichorhinically. The delay (100 to 400 ms) did not influence intensity perception, indicating that intensities are integrated during the sniff irrespective of the temporal arrangement. In contrast, the number of qualities perceived was influenced by the delay: delays of 200 to 400 ms gave significant increases in the frequency of detection of a mixture, whereas synchronous mixtures favoured the perception of a single odour. Masking was also significantly stronger in dichorhinic mixtures. These effects are discussed in terms of retroactive masking which seems to be enhanced by dichorhinic mixtures, suggesting that masking has an important central component.

Adult↗

Olfactory transduction is intrinsically noisy.

The sources of noise that limit olfactory signal detection were investigated in dissociated rat olfactory receptor cells. Near-threshold odorant-evoked currents exhibited large random fluctuation. However, similar fluctuations were observed in the absence of applied odorants when currents were induced by elevating the intracellular cyclic AMP concentration. This suggests that the fluctuations reflect noise intrinsic to the transduction mechanism, rather than the quantal nature of an odorant stimulus. For many odorants, this intrinsic noise may preclude the reliable detection of single odorant molecules.

1-Methyl-3-isobutylxanthine↗

Novel role of cold/menthol-sensitive transient receptor potential melastatine family member 8 (TRPM8) in the activation of store-operated channels in LNCaP human prostate cancer epithelial cells.

Recent cloning of a cold/menthol-sensitive TRPM8 channel (transient receptor potential melastatine family member 8) from rodent sensory neurons has provided the molecular basis for the cold sensation. Surprisingly, the human orthologue of rodent TRPM8 also appears to be strongly expressed in the prostate and in the prostate cancer-derived epithelial cell line, LNCaP. In this study, we show that despite such expression, LNCaP cells respond to cold/menthol stimulus by membrane current (I(cold/menthol)) that shows inward rectification and high Ca(2+) selectivity, which are dramatically different properties from "classical" TRPM8-mediated I(cold/menthol). Yet, silencing of endogenous TRPM8 mRNA by either antisense or siRNA strategies suppresses both I(cold/menthol) and TRPM8 protein in LNCaP cells. We demonstrate that these puzzling results arise from TRPM8 localization not in the plasma, but in the endoplasmic reticulum (ER) membrane of LNCaP cells, where it supports cold/menthol/icilin-induced Ca(2+) release from the ER with concomitant activation of plasma membrane (PM) store-operated channels (SOC). In contrast, GFP-tagged TRPM8 heterologously expressed in HEK-293 cells target the PM. We also demonstrate that TRPM8 expression and the magnitude of SOC current associated with it are androgen-dependent. Our results suggest that the TRPM8 may be an important new ER Ca(2+) release channel, potentially involved in a number of Ca(2+)- and store-dependent processes in prostate cancer epithelial cells, including those that are important for prostate carcinogenesis, such as proliferation and apoptosis.

Animals↗

Biotransformation of 1,8-cineole in the brushtail possum (Trichosurus vulpecula).

1. The metabolic fate of 1,8-cineole was investigated in the brushtail possum. Six possums were fed an artificial diet to which 0.5% 1,8-cineole (wet weight) was added for 2 days. Urine and faeces were collected after the second day. A sample of each was extracted into ethyl acetate and analysed for metabolites. Both free and total levels of metabolites were identified by GC-MS and LC-MS and quantified by GC-MS. 2. The pattern of metabolite excretion was very complex in the brushtail possum. Nineteen metabolites were found in total. Metabolites were categorized into four groups according to the oxidation they had undergone: hydroxycineoles (n = 3), cineolic acids (n = 2), dihydroxycineoles (n = 3) and hydroxycineolic acids (n = 11). No hydroxycineolic acid metabolites have been previously reported as metabolites of 1,8-cineole. 3. Fractional recovery of the ingested dose (2.4 +/- 0.5 g; mean +/- SD) was 0.44 +/- 0.14 (mean +/- SD) in 24 h. Sixty percent of excreted metabolites were hydroxycineolic acids, the most extensively oxidized metabolites. Conjugation with glucuronic acid was inversely related to metabolite polarity, being greatest for hydroxycineoles (41-82%) and minimal for hydroxycineolic acids. 4. Traces of most metabolites were also found in the faeces.

Animals↗

Metabolic fate of S-(-)-pulegone in rat.

1. S-(-)-pulegone was administered orally to rat (250 mg/kg) and the nature of the urinary metabolites was investigated. Eleven metabolites, namely S-(-)-menthofuran, piperitone, piperitenone, p-cresol, 5-hydroxypulegone, 4-methylcyclohexenone, 3-methylcyclohexanone, isopulegone, pulegol, 7-hydroxypiperitone and benzoic acid, have been isolated from rat urine. It is assumed that menthofuran, isopulegone and 4-methylcyclohexenone retain the stereochemistry of the parent compound, whereas in other metabolites the stereochemistry at the asymmetric centres is not known. 2. The relative amounts of various major metabolites present in the total urine extracts from the R-(+) and S-(-)-pulegone-treated rat were established by glc analyses. Urine samples of rats treated with R-(+)-pulegone contained higher levels of p-cresol and piperitenone than in similar experiment carried out with S-(-)-pulegone, whereas the levels of unmetabolized pulegone, piperitone and benzoic acid were considerably higher in the urine of rat treated with S-(-)-pulegone than in a corresponding experiment with R-(+)-pulegone. 3. Phenobarbital-induced rat liver microsomes converted S-(-)-pulegone to S-(-)-menthofuran (VII) and piperitenone (III) in the presence of NADPH and O2. The levels of VII and III were significantly higher in similar experiments carried out with R-(+)-pulegone. 4. Based on these studies, metabolic pathways for the biotransformation of S-(-)-pulegone in rat have been proposed and possible reasons for the observed difference in the toxicity mediated by these two enantiomers are discussed.

Animals↗