224 research outputs found
Elinor Leven, Janice Finkelstein, Ron Tikofsky, Thomas Bodenheimer, Jeffrey Gillman, David S. Dolowitz, Steven Rosen, Frances Shlafer, Sydney Carson, Marcia Alder, Laura Lovinger, Rabbi Mordecai Podet, Judy Lovinger, Joan Schwartz
No full textBlack and white photograph of Elinor Leven, Janice Finkelstein, Ron Tikofsky, Thomas Bodenheimer, Jeffrey Gillman, David S. Dolowitz, Steven Rosen, Frances Shlafer, Sydney Carson, Marcia Alder, Laura Lovinger, Rabbi Mordecai Podet, Judy Lovinger, and Joan Schwartz
Addiction medicine for health care professionals /
No full textIncludes bibliographical references and index.Online resource; title from PDF title page (ScienceDirect, viewed July 8, 2019).Elsevie
Rat group I Metabotropic Glutamate Receptors Inhibit Neuronal Ca<sup>2+</sup>Channels via Multiple Signal Transduction Pathways in HEK 293 Cells
No full textMcCool, Brian A., Jean-Phillipe Pin, Michael M. Harpold, Paul F. Brust, Kenneth A. Stauderman, and David M. Lovinger. Rat group I metabotropic glutamate receptors inhibit neuronal Ca2+channels via multiple signal transduction pathways in HEK 293 cells. J. Neurophysiol. 79: 379–391, 1998. We have shown previously that metabotropic glutamate receptors with group I-like pharmacology couple to N-type and P/Q-type calcium channels in acutely isolated cortical neurons using G proteins most likely belonging to the Gi/Gosubclass. To better understand the potential mechanisms forming the basis for group I mGluR modulation of voltage-gated calcium channels in the CNS, we have examined the ability of specific mGluRs to couple to neuronal N-type (α1B-1/α2δ/β1b) and P/Q-type (α1A-2/α2δ/β1b) voltage-gated calcium channels in an HEK 293 heterologous expression system. Using the whole cell patch-clamp technique where intracellular calcium is buffered to low levels, we have shown that group I receptors inhibit both N-type and P/Q-type calcium channels in a voltage-dependent fashion. Similar to our observations in cortical neurons, this voltage-dependent inhibition is mediated almost entirely by N-ethylmaleimide (NEM)-sensitive heterotrimeric G proteins, strongly suggesting that these receptors can use Gi/Go-like G proteins to couple to N-type and P/Q-type calcium channels. However, inconsistent with the apparent NEM sensitivity of group I modulation of calcium channels, modulation of N-type channels in group I mGluR-expressing cells was only partially sensitive to pertussis toxin (PTX), indicating the potential involvement of both PTX-sensitive and -resistant G proteins. The PTX-resistant modulation was voltage dependent and entirely resistant to NEM and cholera toxin. A time course of treatment with PTX revealed that this toxin caused group I receptors to slowly shift from using a primarily NEM-sensitive G protein to using a NEM-resistant form. The PTX-induced switch from NEM-sensitive to -resistant modulation was also dependent on protein synthesis, indicating some reliance on active cellular processes. In addition to these voltage-dependent pathways, perforated patch recordings on group I mGluR-expressing cells indicate that another slowly developing, calcium-dependent form of modulation for N-type channels may be seen when intracellular calcium is not highly buffered. We conclude that group I mGluRs can modulate neuronal Ca2+channels using a variety of signal transduction pathways and propose that the relative contributions of different pathways may exemplify the diversity of responses mediated by these receptors in the CNS.</jats:p
Cocaine supersensitivity and enhanced motivation for reward in mice lacking dopamine D2 autoreceptors
No full textDopamine (DA) D2 receptors expressed in DA neurons (D 2 autoreceptors) exert a negative feedback regulation that reduces DA neuron firing, DA synthesis and DA release. As D2 receptors are mostly expressed in postsynaptic neurons, pharmacological and genetic approaches have been unable to definitively address the in vivo contribution of D 2 autoreceptors to DA-mediated behaviors. We found that midbrain DA neurons from mice deficient in D2 autoreceptors (Drd2 loxP/loxP; Dat+/IREScre, referred to as autoDrd2KO mice) lacked DA-mediated somatodendritic synaptic responses and inhibition of DA release. AutoDrd2KO mice displayed elevated DA synthesis and release, hyperlocomotion and supersensitivity to the psychomotor effects of cocaine. The mice also exhibited increased place preference for cocaine and enhanced motivation for food reward. Our results highlight the importance of D 2 autoreceptors in the regulation of DA neurotransmission and demonstrate that D2 autoreceptors are important for normal motor function, food-seeking behavior, and sensitivity to the locomotor and rewarding properties of cocaine.Fil: Bello Gay, Estefania Pilar. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Mateo, Yolanda. National Institutes of Health; Estados UnidosFil: Gelman, Diego Matias. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Noain, Daniela Maria Clara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Shin, Jung H.. National Institutes of Health; Estados UnidosFil: Low, Malcolm J.. University of Michigan Medical School; Estados UnidosFil: Alvarez, Veronica A.. National Institutes of Health; Estados UnidosFil: Lovinger, David M.. National Institutes of Health; Estados UnidosFil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentin
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