31 research outputs found
Robust photoregulation of GABA(A) receptors by allosteric modulation with a propofol analogue.
Photochemical switches represent a powerful method for improving pharmacological therapies and controlling cellular physiology. Here we report the photoregulation of GABA(A) receptors (GABA(A)Rs) by a derivative of propofol (2,6-diisopropylphenol), a GABA(A)R allosteric modulator, which we have modified to contain photoisomerizable azobenzene. Using α(1)β(2)γ(2) GABA(A)Rs expressed in Xenopus laevis oocytes and native GABA(A)Rs of isolated retinal ganglion cells, we show that the trans-azobenzene isomer of the new compound (trans-MPC088), generated by visible light (wavelengths ~440 nm), potentiates the γ-aminobutyric acid-elicited response and, at higher concentrations, directly activates the receptors. cis-MPC088, generated from trans-MPC088 by ultraviolet light (~365 nm), produces little, if any, receptor potentiation/activation. In cerebellar slices, MPC088 co-applied with γ-aminobutyric acid affords bidirectional photomodulation of Purkinje cell membrane current and spike-firing rate. The findings demonstrate photocontrol of GABA(A)Rs by an allosteric ligand, and open new avenues for fundamental and clinically oriented research on GABA(A)Rs, a major class of neurotransmitter receptors in the central nervous system
Molecular and Supramolecular Chemistry of Natural Products and Their Model Compounds By Jürgen-Hinrich Fuhrhop (Free University of Berlin) and Claus Endisch (Berlin, Germany). Marcel Dekker: New York. 2000. x + 602 pp. $195.00. ISBN 0-8247-8201-1
Comprehensive and Uniform Synthesis of All Naturally Occurring Phosphorylated Phosphatidylinositols
A Novel Calcium-Dependent Bacterial Phosphatidylinositol-Specific Phospholipase C Displaying Unprecedented Magnitudes of Thio Effect, Inverse Thio Effect, and Stereoselectivity
Unique Catalytic Mechanism of Phosphatidylinositol-Specific Phospholipase C from Streptomyces antibioticus
Mechanism of Phosphatidylinositol−Phospholipase C. 2. Reversal of a Thio Effect by Site-Directed Mutagenesis 1
Potentiating Action of Propofol at GABAA Receptors of Retinal Bipolar Cells
In this study, the authors show that propofol, a widely used anesthetic, exerts a marked and selective potentiation on GABAA receptors of retinal bipolar cells