Supraspinal Gbetagamma-dependent stimulation of PLCbeta originating from G inhibitory protein-mu opioid receptor-coupling is necessary for morphine induced acute hyperalgesia.

Although alterations in μ-opioid receptor signaling mediate excitatory effects of opiates in opioid tolerance, the molecular mechanism for the excitatory effect of acute low dose morphine, as it relates to μ-opioid receptor coupling, is presently unknown. A pronounced coupling of μ-opioid receptor to the α subunit of G inhibitory protein emerged in periaqueductal gray from mice systemically administered with morphine at a dose producing acute thermal hyperalgesia. This coupling was abolished in presence of the selective μ-opioid receptor receptor antagonist CTOP administered at the periaqueductal gray site, showing that the low dose morphine effect is triggered by μ-opioid receptor activated G inhibitory protein at supraspinal level. When Gβγ downstream signalling was blocked by intra-periaqueductal gray co-administration of M119, a compound that inhibits Gβγ dimer-dependent signaling, a complete prevention of low dose morphine induced acute thermal hyperalgesia was obtained. Phospholipase C β3, an enzyme necessary to morphine hyperalgesia, was revealed to be associated with Gβγ in periaqueductal gray. Although opioid administration induces a shift in μ-opioid receptor-G protein coupling from Gi to Gs after chronic administration, our data support that this condition is not realized in acute treatment providing evidence that a separate molecular mechanism underlies morphine induced acute excitatory effect

Magnetotransport in graphene on silicon side of SiC

We have studied the transport properties of graphene grown on silicon side of SiC. Samples under study have been prepared by two different growth methods in two different laboratories. Magnetoresistance and Hall resistance have been measured at temperatures between 4 and 100 K in resistive magnet in magnetic fields up to 22 T. In spite of differences in sample preparation, the field dependence of resistances measured on both sets of samples exhibits two periods of magneto-oscillations indicating two different parallel conducting channels with different concentrations of carriers. The semi-quantitative agreement with the model calculation allows for conclusion that channels are formed by high-density and low-density Dirac carriers. The coexistence of two different groups of carriers on the silicon side of SiC was not reported before.Comment: 5 pages, 6 figures, accepted for publication in the "IOP Journal of Physics: Conference series" as a contribution to the proceedings of the 20th International Conference on "High Magnetic Fields in Semiconductor Physics", HMF 2

A Novel Gβγ-Subunit Inhibitor Selectively Modulates μ-Opioid- Dependent Antinociception and Attenuates Acute Morphine-Induced Antinociceptive Tolerance and Dependence

The Gβγ subunit has been implicated in many downstream signaling events associated with opioids. We previously demonstrated that a small molecule inhibitor of Gβγ-subunit-dependent phospholipase (PLC) activation potentiated morphine-induced analgesia (Bonacci et al., 2006). Here, we demonstrate that this inhibitor, M119 (cyclohexanecarboxylic acid [2-(4,5,6-trihydroxy-3-oxo-3H-xanthen-9-yl)-(9Cl)]), is selective for μ-opioid receptor-dependent analgesia and has additional efficacy in mouse models of acute tolerance and dependence. When administered by an intracerebroventricular injection in mice, M119 caused 10-fold and sevenfold increases in the potencies of morphine and the μ-selective peptide, DAMGO, respectively. M119 had little or no effect on analgesia induced by the κ agonist U50,488 or δ agonists DPDPE or Deltorphin II. Similar results were obtained in vitro, as only activation of the μ-opioid receptor stimulated PLC activation, whereas no effect was seen with the κ- and δ-opioid receptors. M119 inhibited μ-receptor-dependent PLC activation. In studies to further explore the in vivo efficacy of M119, systemic administration M119 also resulted in a fourfold shift increase in potency of systemically administered morphine. Of particular interest, M119 was also able to attenuate acute, antinociceptive tolerance and dependence in mice treated concomitantly with both M119 and morphine. These studies suggest that small organic molecules, such as M119, that specifically regulate Gβγ subunit signaling may have important therapeutic applications in enhancing opioid analgesia, while attenuating the development of tolerance and dependence

Evaluation of the optical conductivity tensor in terms of contour integrations

For the case of finite life-time broadening the standard Kubo-formula for the optical conductivity tensor is rederived in terms of Green's functions by using contour integrations, whereby finite temperatures are accounted for by using the Fermi-Dirac distribution function. For zero life-time broadening, the present formalism is related to expressions well-known in the literature. Numerical aspects of how to calculate the corresponding contour integrals are also outlined.Comment: 8 pages, Latex + 2 figure (Encapsulated Postscript

From laterally modulated two-dimensional electron gas towards artificial graphene

Cyclotron resonance has been measured in far-infrared transmission of GaAs/Al$_x$Ga$_{1-x}$As heterostructures with an etched hexagonal lateral superlattice. Non-linear dependence of the resonance position on magnetic field was observed as well as its splitting into several modes. Our explanation, based on a perturbative calculation, describes the observed phenomena as a weak effect of the lateral potential on the two-dimensional electron gas. Using this approach, we found a correlation between parameters of the lateral patterning and the created effective potential and obtain thus insights on how the electronic miniband structure has been tuned. The miniband dispersion was calculated using a simplified model and allowed us to formulate four basic criteria that have to be satisfied to reach graphene-like physics in such systems

PLCε1 suppresses tumor growth by regulating murine T cell mobilization

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154282/1/cei13409.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154282/2/cei13409_am.pd

In-Plane Magnetic Field Induced Anisotropy of 2D Fermi Contours and the Field Dependent Cyclotron Mass

The electronic structure of a 2D gas subjected to a tilted magnetic field, with a strong component parallel to the GaAs/AlGaAs interface and a weak component oriented perpendicularly, is studied theoretically. It is shown that the parallel field component modifies the originally circular shape of a Fermi contour while the perpendicular component drive an electron by the Lorentz force along a Fermi line with a cyclotron frequency given by its shape. The corresponding cyclotron effective mass is calculated self-consistently for several concentrations of 2D carriers as a function of the in-plane magnetic field. The possibility to detect its field-induced deviations from the zero field value experimentally is discussed.Comment: written in LaTeX, 9 pages, 4 figures (6 pages) in 1 PS file (compressed and uuencoded) available on request from [email protected], SM-JU-93-

Transverse Magnetoresistance of GaAs/AlGaAs Heterojunctions in the Presence of Parallel Magnetic Fields

We have calculated the resistivity of a GaAs\slash AlGaAs heterojunction in the presence of both an in--plane magnetic field and a weak perpendicular component using a semiclassical Boltzmann transport theory. These calculations take into account fully the distortion of the Fermi contour which is induced by the parallel magnetic field. The scattering of electrons is assumed to be due to remote ionized impurities. A positive magnetoresistance is found as a function of the perpendicular component, in good qualitative agreement with experimental observations. The main source of this effect is the strong variation of the electronic scattering rate around the Fermi contour which is associated with the variation in the mean distance of the electronic states from the remote impurities. The magnitude of the positive magnetoresistance is strongly correlated with the residual acceptor impurity density in the GaAs layer. The carrier lifetime anisotropy also leads to an observable anisotropy in the resistivity with respect to the angle between the current and the direction of the in--plane magnetic field.Comment: uuencoded file containing a 26 page RevTex file and 14 postscript figures. Submitted to Phys. Rev.

G protein βγ subunits regulate cardiomyocyte hypertrophy through a perinuclear Golgi phosphatidylinositol 4-phosphate hydrolysis pathway.

We recently identified a novel GPCR-dependent pathway for regulation of cardiac hypertrophy that depends on Golgi phosphatidylinositol 4-phosphate (PI4P) hydrolysis by a specific isoform of phospholipase C (PLC), PLCε, at the nuclear envelope. How stimuli are transmitted from cell surface GPCRs to activation of perinuclear PLCε is not clear. Here we tested the role of G protein βγ subunits. Gβγ inhibition blocked ET-1-stimulated Golgi PI4P depletion in neonatal and adult ventricular myocytes. Blocking Gβγ at the Golgi inhibited ET-1-dependent PI4P depletion and nuclear PKD activation. Translocation of Gβγ to the Golgi stimulated perinuclear Golgi PI4P depletion and nuclear PKD activation. Finally, blocking Gβγ at the Golgi or PM blocked ET-1-dependent cardiomyocyte hypertrophy. These data indicate that Gβγ regulation of the perinuclear Golgi PI4P pathway and a separate pathway at the PM is required for ET-1-stimulated hypertrophy, and the efficacy of Gβγ inhibition in preventing heart failure maybe due in part to its blocking both these pathways

Density of states and electron concentration of double heterojunctions subjected to an in-plane magnetic field

We calculate the electronic states of Al$_x$Ga$_{1-x}$As/GaAs/Al$_x$Ga$_{1-x}$As double heterojunctions subjected to a magnetic field parallel to the quasi two-dimensional electron gas. We study the energy dispersion curves, the density of states, the electron concentration and the distribution of the electrons in the subbands. The parallel magnetic field induces severe changes in the density of states, which are of crucial importance for the explanation of the magnetoconductivity in these structures. However, to our knowledge, there is no systematic study of the density of states under these circumstances. We attempt a contribution in this direction. For symmetric heterostructures, the depopulation of the higher subbands, the transition from a single to a bilayer electron system and the domination of the bulk Landau levels in the centre the wide quantum well, as the magnetic field is continuously increased, are presented in the ``energy dispersion picture'' as well as in the ``electron concentration picture'' and in the ``density of states picture''.Comment: J. Phys.: Condens. Matter 11 No 26 (5 July 1999) 5131-5141 Figures (three) embedde