Evidence for an olfactory receptor which responds to nicotine — nicotine as an odorant

Summary The tobacco alkaloid (S)(–)-nicotine, when applied as a vapour to an in vitro head preparation, stimulates the olfactory epithelium in three strains of rats and to a lesser extent in two strains of mice. The electro-olfactogram (EOG) generated by nicotine has similar characteristics to the EOGs produced by known odorants. The nicotine EOG increases with increasing concentration of nicotine vapour (1–100 nM) applied to the olfactory epithelium.Differential reduction of the nicotine EOG by the lectin concanavalin A is seen in Wistar and Lister Hooded rats. The reduction of the nicotine EOG by concanavalin A is prevented by adding alpha-methyl-D-mannoside to the lectin superfusion medium. This suggests that there is a glyco-moiety associated with at least one olfactory receptor responding to nicotine.Our results suggest that rat olfactory epithelium has receptor sites for nicotine. Nicotine is an unusual compound because it shows both odorant and pharmacological properties.22 September 1986     

A newTrichoplusia ni antennal receptor neuron that responds to attomolar concentrations of a minor pheromone component

Summary A newly discovered third class of sensillum trichodea on the antenna ofTrichoplusia ni contains an olfactory receptor neuron that responds to (Z)-9-tetradecen-1-ol acetate at 1×10^–18 M. The threshold of this neuron is 100–1000 times lower than the thresholds of two previously described pheromone-sensitive neurons that detect (Z)-7-dodecen-1-ol acetate and (Z)-7-tetradecen-1-ol acetate. The sensitivity and selectivity of this receptor neuron is evidence that (Z)-9-tetradecen-1-ol acetate may be important for sexual behavior.     

Evidence that prokineticin receptor 2 exists as a dimer in vivo

Prokineticins are proteins that regulate diverse biological processes including gastrointestinal motility, angiogenesis, circadian rhythm, and innate immune response. Prokineticins bind two closed related G-protein coupled receptors (GPCRs), PKR1 and PKR2. In general, these receptors act as molecular switches to relay activation to heterotrimeric G-proteins and a growing body of evidence points to the fact that GPCRs exist as homo- or heterodimers. We show here by Western-blot analysis that PKR2 has a dimeric structure in neutrophils. By heterologous expression of PKR2 in Saccharomyces cerevisiae, we examined the mechanisms of intermolecular interaction of PKR2 dimerization. The potential involvement of three types of mechanisms was investigated: coiled-coil, disulfide bridges, and hydrophobic interactions between transmembrane domains. Characterization of differently deleted or site-directed PKR2 mutants suggests that dimerization proceeds through interactions between transmembrane domains. We demonstrate that co-expressing binding-deficient and signaling-deficient forms of PKR2 can re-establish receptor functionality, possibly through a domain-swapping mechanism.     

Evidence for the existence of an agent in the serum of the cyclic hematopoietic dog which influences hemoglobin synthesis

Summary Serum samples collected through the cycle of a cyclic hematopoietic (CH) dog under reduced atmospheric conditions, were assayed for their ability to affect hemoglobin synthesis by normal canine bone marrow. Varying levels of hemoglobin synthesis in the presence of different serum samples suggest an agent cycles in the serum of CH dogs which influences hemoglobin synthesis.     

Piroxicam-induced analgesia: Evidence for a central component which is not opioid mediated

Piroxicam is a nonsteroidal anti-inflammatory drug with a potent analgesic effect. In order to establish whether the analgesic action of Piroxicam has a central component, we studied the effect of the drug on the nociceptive orbicularis oculi reflexes evoked by electrical stimulation of the cornea and supraorbital nerve in healthy subjects. Piroxicam significantly suppressed the corneal reflex and R3 component of the blink reflex by 28% (p<0.05) and 50% (p<0.01), respectively. This effect was not reversed by the i.v. injection of naloxone. Beta-endorphin levels did not change. Piroxicam administration induces distinct inhibitory changes in nociceptive reflexes, which suggests that the analgesic action of the drug has a central component. The ineffectiveness of naloxone, and the lack of beta-endorphin changes, indicate that this central action is independent of the opioid system; other pain regulatory systems are probably involved.     

Evidence for an aphrodisiac pheromone of femaleDrosophila

Summary We report here direct evidence for the involvement of a pheromone in the induction of male wing vibration, an important fixed action of theDrosophila melanogaster courtship pattern. This chemical stimulus is produced by mature females but not by mature males. The behavioral response is proportional to the pheromone concentration.Acknowledgments. Thanks are due to Drs Y. Hotta, S. Benzer and C. Descoins for stimulating discussions at the beginning of this work. Most of it was performed in the Centre de Génétique Moléculaire du C.N.R.S. We want to acknowledge their financial support.     

Evidence for differences in alpha-adrenergic receptor affinity in stress susceptible swine

Summary pA₂-Values were determined using phentolamine-methoxamine. The mean pA₂-value on aortic strips from stress susceptible swine was 7.81 and 7.39 for control. The -adrenergic receptor from stress susceptible swine has a higher affinity than that of control.Acknowledgments. The author appreciates the cooperation of Dr L. L. Christian and the Meat Laboratory in obtaining the tissues and the technical assistance of Vern Hoyt.     

Evidence for an adipokinetic mechanism in the ventromedial hypothalamus

Zusammenfassung Nach peroraler Verabreichung von¹⁴C-Glukose konnte in den Lipiden des ventromedialen Hypothalamus mehr Radioaktivität nachgewiesen werden als im lateralen Hypothalamus. Dies könnte ein Hinweis für eine Steuerung der Nahrungsaufnahme über den Lipidmetabolismus des medialen Hypothalamus sein.     

Evidence for an unusual multifunctional protoreceptor in hormone action

Summary Contrary to the techniques of mere association, column chromatography has revealed a protoreceptor that accepts aldosterone agonists and antagonists only in the physiological target, the kidney, and is absent in non-targets, liver and serum; it is furthermore different from the aldosterone specific receptor in renal cytosol.Supported in part by grants from the CNRS AI 03 1917 and UER Broussais Hôtel Dieu.     

Prefrontal cortex of the cat: Evidence for an additional area

Summary Direct projections from the mediodorsal nucleus of the thalamus to ventral parts of the insular region of the cat's cortex were demonstrated by using the horseradish peroxidase technique.     

Evidence for a constant number of available sweet receptor sites at threshold concentrations of sugars

Summary Intensity/time plots of sweetness produced by different molecules allow putative accession efficiencies of these molecules and their affinities with the taste receptor to be calculated. Results suggest that affinities of the different molecules are in the same order as threshold concentrations and that a constant number of available receptors exist for a related family of structures near threshold concentrations.     

Old drugs with new skills: fenoprofen as an allosteric enhancer at melanocortin receptor 3

The efficiency of drug research and development has paradoxically declined over the last decades despite major scientific and technological advances, promoting new cost-effective strategies such as drug repositioning by systematic screening for new actions of known drugs. Here, we performed a screening for positive allosteric modulators (PAMs) at melanocortin (MC) receptors. The non-steroidal anti-inflammatory drug fenoprofen, but not the similar compound ibuprofen, presented PAM activity at MC₃, MC₄, and MC₅ receptors. In a model of inflammatory arthritis, fenoprofen afforded potent inhibition while ibuprofen was nearly inactive. Fenoprofen presented anti-arthritic actions on cartilage integrity and synovitis, effects markedly attenuated in Mc3r?/? mice. Fenoprofen displayed pro-resolving properties promoting macrophage phagocytosis and efferocytosis, independently of cyclooxygenase inhibition. In conclusion, combining repositioning with advances in G-protein coupled receptor biology (allosterism) may lead to potential new therapeutics. In addition, MC₃ PAMs emerged as a viable approach to the development of innovative therapeutics for joint diseases.     

Evidence for an intracytoplasmic membrane in the core of spores ofBacillus popilliae

Zusammenfassung Die Arbeit bringt den elektronenmikroskopischen Beweis für das Bestehen einer intracytoplasmatischen Membran im Cytoplasma (core) der Sporen vonBacillus popilliae.

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This investigation was supported by a research contract from the Northern Utilization Research and Development Division, US Department of Agriculture, Peoria (Illinois).     

Coordinated shift of olfactory amino acid responses and V2R expression to an amphibian water nose during metamorphosis

All olfactory receptors identified in teleost fish are expressed in a single sensory surface, whereas mammalian olfactory receptor gene families segregate into different olfactory organs, chief among them the main olfactory epithelium expressing ORs and TAARs, and the vomeronasal organ expressing V1Rs and V2Rs. A transitional stage is embodied by amphibians, with their vomeronasal organ expressing more ‘modern’, later diverging V2Rs, whereas more ‘ancient’, earlier diverging V2Rs are expressed in the main olfactory epithelium. During metamorphosis, the main olfactory epithelium of Xenopus tadpoles transforms into an air-filled cavity (principal cavity, air nose), whereas a newly formed cavity (middle cavity) takes over the function of a water nose. We report here that larval expression of ancient V2Rs is gradually lost from the main olfactory epithelium as it transforms into the air nose. Concomitantly, ancient v2r gene expression begins to appear in the basal layers of the newly forming water nose. We observe the same transition for responses to amino acid odorants, consistent with the hypothesis that amino acid responses may be mediated by V2R receptors.     

Response to an antiestrogen as a criterion for hormonal sensitivity of endometrial cancer]

A test is described for the evaluation of hormone sensitivity of endometrial cancer in vivo. The concentrations of progesterone and estradiol receptors, and the activities of ornithine-decarboxylase and 17 beta-hydroxysteroid oxido-reductase enzymes have been measured in the tumor, before and after administration of the anti-estrogen tamoxifen. The responses observed, in particular the increase of progesterone receptor, could allow a more rational approach to hormonal therapy of endometrial cancer.     

Access to the odor world: olfactory receptors and their role for signal transduction in insects

The sense of smell enables insects to recognize and discriminate a broad range of volatile chemicals in their environment originating from prey, host plants and conspecifics. These olfactory cues are received by olfactory sensory neurons (OSNs) that relay information about food sources, oviposition sites and mates to the brain and thus elicit distinct odor-evoked behaviors. Research over the last decades has greatly advanced our knowledge concerning the molecular basis underlying the reception of odorous compounds and the mechanisms of signal transduction in OSNs. The emerging picture clearly indicates that OSNs of insects recognize odorants and pheromones by means of ligand-binding membrane proteins encoded by large and diverse families of receptor genes. In contrast, the mechanisms of the chemo-electrical transduction process are not fully understood; the present status suggests a contribution of ionotropic as well as metabotropic mechanisms. In this review, we will summarize current knowledge on the peripheral mechanisms of odor sensing in insects focusing on olfactory receptors and their specific role in the recognition and transduction of odorant and pheromone signals by OSNs.