scholarly journals Definition of two agonist types at the mammalian cold-activated channel TRPM8

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Annelies Janssens ◽  
Maarten Gees ◽  
Balazs Istvan Toth ◽  
Debapriya Ghosh ◽  
Marie Mulier ◽  
...  

Various TRP channels act as polymodal sensors of thermal and chemical stimuli, but the mechanisms whereby chemical ligands impact on TRP channel gating are poorly understood. Here we show that AITC (allyl isothiocyanate; mustard oil) and menthol represent two distinct types of ligands at the mammalian cold sensor TRPM8. Kinetic analysis of channel gating revealed that AITC acts by destabilizing the closed channel, whereas menthol stabilizes the open channel, relative to the transition state. Based on these differences, we classify agonists as either type I (menthol-like) or type II (AITC-like), and provide a kinetic model that faithfully reproduces their differential effects. We further demonstrate that type I and type II agonists have a distinct impact on TRPM8 currents and TRPM8-mediated calcium signals in excitable cells. These findings provide a theoretical framework for understanding the differential actions of TRP channel ligands, with important ramifications for TRP channel structure-function analysis and pharmacology.

2016 ◽  
Vol 82 (8) ◽  
pp. 2467-2478 ◽  
Author(s):  
Laura Terrón-González ◽  
Guadalupe Martín-Cabello ◽  
Manuel Ferrer ◽  
Eduardo Santero

ABSTRACTA metagenomic library of a petroleum-contaminated soil was constructed in a fosmid vector that allowed heterologous expression of metagenomic DNA. The library, consisting of 6.5 Gb of metagenomic DNA, was screened for extradiol dioxygenase (Edo) activity using catechol and 2,3-dihydroxybiphenyl as the substrates. Fifty-eight independent clones encoding extradiol dioxygenase activity were identified. Forty-one different Edo-encoding genes were identified. The population of Edo genes was not dominated by a particular gene or by highly similar genes; rather, the genes had an even distribution and high diversity. Phylogenetic analyses revealed that most of the genes could not be ascribed to previously defined subfamilies of Edos. Rather, the Edo genes led to the definition of 10 new subfamilies of type I Edos. Phylogenetic analysis of type II enzymes defined 7 families, 2 of which harbored the type II Edos that were found in this work. Particularly striking was the diversity found in family I.3 Edos; 15 out of the 17 sequences assigned to this family belonged to 7 newly defined subfamilies. A strong bias was found that depended on the substrate used for the screening: catechol mainly led to the detection of Edos belonging to the I.2 family, while 2,3-dihydroxybiphenyl led to the detection of most other Edos. Members of the I.2 family showed a clear substrate preference for monocyclic substrates, while those from the I.3 family showed a broader substrate range and high activity toward 2,3-dihydroxybiphenyl. This metagenomic analysis has substantially increased our knowledge of the existing biodiversity of Edos.


2009 ◽  
Vol 30 (3_suppl3) ◽  
pp. S267-S342 ◽  
Author(s):  
Michael H. Golden

Recommended Nutrient Intakes (RNIs) are set for healthy individuals living in clean environments. There are no generally accepted RNIs for those with moderate malnutrition, wasting, and stunting, who live in poor environments. Two sets of recommendations are made for the dietary intake of 30 essential nutrients in children with moderate malnutrition who require accelerated growth to regain normality: first, for those moderately malnourished children who will receive specially formulated foods and diets; and second, for those who are to take mixtures of locally available foods over a longer term to treat or prevent moderate stunting and wasting. Because of the change in definition of severe malnutrition, much of the older literature is pertinent to the moderately wasted or stunted child. A factorial approach has been used in deriving the recommendations for both functional, protective nutrients (type I) and growth nutrients (type II).


1999 ◽  
Vol 81 (4) ◽  
pp. 1486-1494 ◽  
Author(s):  
Nina S. Bradley

Transformations in embryonic motility in chick: kinematic correlates of type I and II motility at E9 and E12. Soon after hatching, chicks exhibit an array of adaptive, coordinated behaviors. Chick embryos also acquire nearly 18 days of movement experience, referred to as embryonic motility, before hatching. The chick expresses three forms of motility, types I, II, and III, and each emerges at a different stage of embryonic development. Although much is known about the mechanisms associated with motility at early embryonic stages and at the onset of hatching, the transformations in behavior and underlying mechanisms are not fully understood. Thus the purpose of this study was to determine how motility is modified during the first expected transformation, from type I to type II. It was hypothesized that kinematic features for motility at embryonic day 12 (E12) would differ significantly from features at E9 because type II motility emerges during E11. Embryos were video taped for extended intervals in ovo at E9 or E12 and entire sequences of motility were computer digitized for kinematic analyses. Results reported here indicate that several of the kinematic features characteristic of motility at E9 are also reliable features at E12. On the basis of these findings, a kinematic definition of type I motility is posed for use in subsequent behavioral studies. Several parameters distinguished motility at E12 from E9. The most notable difference between ages was the less regular timing of repetitive limb movements at E12, a finding consistent with recent reports suggesting early motility is an emergent product of a transient neural network rather than a specialized pattern generator. As predicted from established definitions for type II motility, startle-like movements were common at E12; however, they also were present in many kinematic plots at E9, suggesting the discreet age-dependent boundaries in the established definition for type II motility may require modification. Some age-related differences, such as increased intralimb coordination and excursion velocity, may be prerequisites for adaptive behavior after hatching.


2011 ◽  
Vol 300 (6) ◽  
pp. R1494-R1505 ◽  
Author(s):  
Noriyuki Mori ◽  
Fuminori Kawabata ◽  
Shigenobu Matsumura ◽  
Hiroshi Hosokawa ◽  
Shigeo Kobayashi ◽  
...  

The transient receptor potential (TRP) channel family is composed of a wide variety of cation-permeable channels activated polymodally by various stimuli and is implicated in a variety of cellular functions. Recent investigations have revealed that activation of TRP channels is involved not only in nociception and thermosensation but also in thermoregulation and energy metabolism. We investigated the effect of intragastric administration of TRP channel agonists on changes in energy substrate utilization of mice. Intragastric administration of allyl isothiocyanate (AITC; a typical TRPA1 agonist) markedly increased carbohydrate oxidation but did not affect oxygen consumption. To examine whether TRP channels mediate this increase in carbohydrate oxidation, we used TRPA1 and TRPV1 knockout (KO) mice. Intragastric administration of AITC increased carbohydrate oxidation in TRPA1 KO mice but not in TRPV1 KO mice. Furthermore, AITC dose-dependently increased intracellular calcium ion concentration in cells expressing TRPV1. These findings suggest that AITC might activate TRPV1 and that AITC increased carbohydrate oxidation via TRPV1.


1974 ◽  
Vol 53 ◽  
pp. 1-46 ◽  
Author(s):  
Soji Kaneyuki ◽  
Tadashi Tsuji

The theory of classification of homogeneous bounded domains in the complex number space Cn has been developed mainly in the recent papers [10], [6], [3] and [7]. As a result, the classification is reduced to that of S-algebras due to Takeuchi [7] which correspond to irreducible Siegel domains of type I or type II (For the definition of irreducibility see § 1). On the other hand Pjateckii-Sapiro [5] found large classes of homogeneous Siegel domains obtained from classical self-dual cones. Even in lower-dimensional cases, however, there are still homogeneous Siegel domains which do not appear in his results.


Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1627
Author(s):  
Lujain Aloum ◽  
Eman Alefishat ◽  
Janah Shaya ◽  
Georg A. Petroianu

Sneezing (sternutatio) is a poorly understood polysynaptic physiologic reflex phenomenon. Sneezing has exerted a strange fascination on humans throughout history, and induced sneezing was widely used by physicians for therapeutic purposes, on the assumption that sneezing eliminates noxious factors from the body, mainly from the head. The present contribution examines the various mixtures used for inducing sneezes (remedia sternutatoria) over the centuries. The majority of the constituents of the sneeze-inducing remedies are modulators of transient receptor potential (TRP) channels. The TRP channel superfamily consists of large heterogeneous groups of channels that play numerous physiological roles such as thermosensation, chemosensation, osmosensation and mechanosensation. Sneezing is associated with the activation of the wasabi receptor, (TRPA1), typical ligand is allyl isothiocyanate and the hot chili pepper receptor, (TRPV1), typical agonist is capsaicin, in the vagal sensory nerve terminals, activated by noxious stimulants.


The relation between X-ray diffracting properties and ultra-violet absorption has been studied point by point on polished plates of diamond having thicknesses from 0-1 mm to more than 1 mm and edge lengths from 2 mm to more than 1 cm. Most specimens exhibit marked non-uniformity of ultra-violet absorption. The intensity of the ‘spike’ X-ray reflexions was found to be roughly proportional to ultra-violet absorption, point by point, a t least in the range of weak and moderate spike intensities. Hence it is concluded that the platelets responsible for the ‘spikes’ are also responsible for the characteristic type I absorptions. However, high values of spike intensity and ultra-violet absorption have only been observed in relatively perfect crystal regions with a low density of grown-in dislocations as determined by X-ray topography; and it is suggested that in imperfect regions containing many grown-in dislocations impurity precipitation in the form of platelets coherent with the matrix may have been inhibited or pre-empted by precipitation in some other way. Thus the absence of ‘ spikes ’ and characteristic type I absorptions may not necessarily imply absence of impurity. On the other hand, some regions of high ultra-violet transparency can be highly perfect; hence lattice imperfection is not necessarily associated with type II optical characteristics. A comparison of ‘spike’ intensity in equivalent cube directions, made on a specimen selected for the high definition of its ‘spike’ topograph features, showed that where platelet precipitation was present it had occurred equally on all cube planes. The sharpness of boundaries between regions of high and low ultra-violet absorption and the association of such boundaries with growth stratifications revealed by Bragg reflexion topographs suggest that they correspond to variations of concentration of grown-in impurity in the crystal, no detectable subsequent diffusion having taken place.


1986 ◽  
Vol 7 ◽  
pp. 599-609
Author(s):  
R. A. Chevalier

AbstractType I supernovae can be modeled as the carbon deflagration of white dwarfs and Type II supernovae as the explosions of massive stars with hydrogen envelopes. The massive stars at the ends of their lives are expected to be red supergiants, which are observed to have slow, dense winds. The interaction of the supernova kinetic energy and radiation with the circumstellar gas gives rise to observational phenomena at a range of wavelengths. Additional phenomena, such as a scattered light echo, are predicted. While the light from a Type II supernova near maximum light is probably from energy deposited in the initial explosion, there is now good evidence that the radioactive decay of 56Co powers the emission at late times. It was been noted that the explosions of massive stars without hydrogen envelopes would be quite unlike normal Type II supernovae. There is now good evidence for such explosions – SN1985f and the class of peculiar Type I supernovae. It is suggested that these supernovae be called Type III with the spectroscopic definition of a) no H lines and b) broad [01] lines at late times. That not all very massive star explosions are of this type is indicated by SN1961v, which was probably a very massive explosion, but in which hydrogen was present.


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