DOCSLIB.ORG

Multiple GABA Receptor Subtypes Mediate Inhibition of Calcium Influx at Rat Retinal Bipolar Cell Terminals

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Multiple GABA Receptor Subtypes Mediate Inhibition of Calcium Influx at Rat Retinal Bipolar Cell Terminals The Journal of Neuroscience, April 1995, 75(4): 2668-2679 Multiple GABA Receptor Subtypes Mediate Inhibition of Calcium Influx at Rat Retinal Bipolar Cell Terminals Zhuo-Hua Pan’ and Stuart A. Lipton* 1Department of Neurology, Children’s Hospital and Harvard Medical School, Boston, Massachusetts 02115 and *Department of Neurology, Children’s Hospital, Beth Israel Hospital, Brigham and Women’s Hospital, Massachusetts General Hospital, and Program in Neuroscience, Harvard Medical School, Boston, Massachusetts 02115 Inhibitory effects of GABA on K+-evoked Ca2+ influx into sensitiveto GABA (Tachibanaand Kaneko, 1987; Karschin and rat retinal bipolar cell terminals were studied using calcium Wbsle, 1990; Suzuki et al., 1990; Yeh et al., 1990; Heidelberger imaging methods. Application of high K+ evokes a sus- and Matthews, 1991). It is speculatedthat the input of GA- tained, reversible increase in [Ca2+li at bipolar cell termi- BAergic amacrinecells to bipolar cell terminalscreates negative nals, which occurs mainly via dihydropyridine-sensitive (L- feedback to generate transient responsesin the inner retina type) Ca2+ channels. There are at least two GABA receptor (Tachibanaand Kaneko, 1987; Maguire et al., 1989). subtypes coexisting at bipolar cell terminals: a convention- Recently, a novel bicuculline/baclofen-insensitiveGABA re- al GABA, receptor and a bicuculline/baclofen-insensitive ceptor has been reported on tectal neuronesof the frog (Nistri GABA receptor. Activation of either GABA receptor inhib- and Sivilotti, 1985; Sivilotti and Nistri, 1989) and retinal neu- ited the K+-evoked Ca*+ response. However, these two rons in several species(Feigenspan et al., 1993; Qian and Dowl- GABA receptor subtypes have distinct properties. GABA, ing, 1993; Dong et al., 1994; Lukasiewicz et al., 1994; Matthews receptors suppress the Ca*+ response only at relatively et al., 1994; Zhang and Slaughter, 1994). The newly cloned GA- high concentrations of agonist, and with fas’ kinetics and BAp subunits and GABAp-like responsesencoded by bovine a narrow dynamic range. In contrast, the bicucullinelbaclo- retinal mRNA, expressedin Xenopus oocytes, display similar fen-insensitive GABA receptors produce inhibition on the properties (Cutting et al., 1991; Polenzani et al., 1991; Shimada Caz+ response at a much lower concentration of agonist, et al., 1992; Kusamaet al., 1993b). This novel GABA receptor and with slow onset and a wider dynamic range. The phar- is commonly referred to as the GABA, receptor (Johnston, macologic profile of the bicucullinelbaclofen-insensitive 1986; Shimadaet al., 1992). Although a similar GABA receptor GABA receptor at bipolar cell terminals is most similar to has been found in several species,the GABA, receptor of rat the GABA, receptor reported by Feigenspan et al. (1993). bipolar cells has been reported to be insensitive to picrotoxin Unlike the GABA, receptors described in other species, it (Feigenspanet al., 1993). The implication of this discrepancy is is extremely insensitive to picrotoxin. Therefore, it may be not clear, since the pharmacologic properties and molecular appropriate to refer to this receptor as a picrotoxin-insen- identities of the putative GABA, receptor are still not fully un- sitive GABA, receptor. 3-Aminopropyl(methyl)phosphinic derstood. acid (3-APMPA) and 3-aminopropylphosphonic (3-APA), Very few studieshave examined selective antagonistsfor this two phosphate analogs of GABA, selectively antagonize newly describedGABA receptor or family of receptors.Several the picrotoxin-insensitive GABA, receptors but not the GA- phosphateanalogs of GABA, which are the GABA, receptor BA, receptors in this system. These results imply a func- agonistsor antagonists(Slaughter and Pan, 1992), and imidaz- tional role for multiple GABA receptors in regulating syn- ole-4-acetic acid (14AA), a GABA analog with an extended con- aptic transmission at bipolar cell terminals. formation (Kusamaet al., 1993; Qian and Dowling, 1994), have [Key words: GABA, GABA receptors, calcium, 3-amino- been reported to display antagonistproperties to the bicuculline/ propyl(methyl)phosphinic acid, synaptic transmission, bi- baclofen-insensitiveGABA receptorsexpressed in Xenopus oo- polar cells, retina, rat] cytes (Kusamaet al., 1993a; Woodward et al., 1993). 14AA has also been reported to be an effective antagonistof the GABA, GABA is one of the major inhibitory neurotransmittersin the receptor in fish retinal horizontal cells (Qian and Dowling, CNS in general and in the retina in particular (Olsen and Venter, 1994). However, the properties of these compoundshave not 1986; Massey and Redburn, 1987; Tauck et al., 1988; Sivilotti been studied on the picrotoxin-insensitive type of GABA, re- and Nistri, 1991; Slaughter and Pan, 1992). There is abundant ceptors found in the rat retinal neurons. evidence that the terminals of retinal bipolar cells are highly Recent studies have shown that GABA can act at multiple subtypesof GABA receptorson bipolar cells. Both GABA, and Received Aug. 24, 1994; revised Oct. 13, 1994; accepted Oct. 24, 1994. GABA, receptors have been reported in retinal bipolar cells of We thank Dr. Malcolm M. Slaughter for helpful discussions and valuable comments on the manuscript. This work was supported in part by a Scholar goldfish, rat, tiger salamander,and white perch (Tachibanaand Award from the American Foundation for AIDS Research (to Z.-HI!) and by Kaneko, 1987; Feigenspanet al., 1993; Qian and Dowling, NIH Grant ROl EY05477 (to S.A.L.). 1993b; Lukasiewicz et al., 1994; Matthews et al., 1994). Pre- Correspondence should be addressed to Dr. Zhuo-Hua Pan at the above ad- dress. viously, a baclofen-sensitiveGABA, receptor has been reported Copyright 0 1995 Society for Neuroscience 0270-6474/95/152668-12$05.00/O in tiger salamanderbipolar cell terminals (Maguire et al., 1989). The Journal of Neuroscience, April 1995, 15(4) 2669 In goldhsh bipolar cell terminals, a baclofen-insensitive GA- saturate the fluorescence Ca 2+ indicator. Under our condition, 80 mM BA,-like receptor has also been reported (Heidelberger and Mat- K+ evoked an eouivalent or sometimes slightly smaller fluorescence signal than that eboked by 60 mM K+. However, 40 mM K’ evoked a thews, 1991; Matthews et al., 1994). The common effect of all consistentlv smaller fluorescence signal than 60 mM K+ (85% 2 3%. of these GABA receptors is, in one way or another, to regulate mean 2 SEM, n = 7). In order to-assure that the CaZ+ indicator was the Ca*+ response of the terminal. Although the inhibitory effect not saturated by [Ca*+],, 40 mM K+ was therefore used to evoke Ca2+ of GABA on Ca2+ influx into giant goldfish bipolar terminals responses throughout this work. Pharmacological agents were mixed with high K+ saline and applied by pneumatic (“puffer”) pipettes has been directly visualized with calcium imaging methods (Hei- placed about 3040 pm away from the bipolar cell terminals, unless delberger and Matthews, 1991; Matthews et al., 1994), a detailed otherwise specified. picture of the interaction of multiple GABA receptor subtypes Fluorescence measurement. Fluorescence measurements were per- in regulating Ca*+ responses at bipolar cell terminals, especially formed at room temperature on a confocal laser-scanning microscope in mammalian species, is not clear. Furthermore, the functional (NORAN, WI) coupled to an imaging system (Universal Imaging, PA). The video scan module (Odyssey) was mounted on an upright Nikon significance of the coexistence of GABA receptor subtypes at microscope fitted with a 40X, 0.75 NA water-immersion objective. Op- bipolar cell terminals remains unknown. tical excitation was accomplished using the 488 nm line of an argon In this study, by using calcium imaging, we demonstrated the laser. The emitted fluorescence passed through a 5 15 nm primary barrier colocalization of multiple GABA receptor subtypes at rat bipolar filter before it reached the photomultiplier tube. The laser intensity was minimized to prevent dye bleaching during the course of the experi- cell terminals. Particularly, we further characterized the phar- ments. During measurements, the fluorescence images were acquired in macologic properties of the GABA, receptor and the dynamic real-time mode (30 frames/set), and the fluorescence data at a defined course of inhibition resulting from multiple GABA receptor sub- bipolar cell terminal were stored and later exported to a SIGMAPLOT types at rat bipolar cell terminals. Previous studies have mainly graphics program. In some cases, the real-time video images were di- focused on the responses recorded from the bipolar cell soma. rectly recorded onto an optical memory disc recorder (OMDR, Pana- sonic) for later analysis. An advantage here is that the responses of synaptic terminals Data analysis. Since fluo-3 is a single-wavelength chromophore, the could be directly visualized. fluorescence is a function of the [Ca*+], as well as the dye concentration. A preliminary report of part of this work has appeared (Pan However, for a fixed region, the change of fluorescence directly reflects and Lipton, 1994b). the change of [Ca*+],. Therefore, data are not calibrated to absolute values of ]Ca2+],, but are displayed as a ratio of fluorescence change. Materials and Methods For the purpo&of clarity, we will use the term “calcium” instead of “fluorescence” throughout the uauer. A total of 826 biuolar cell ter- Bipolar cell isolation. Bipolar cells were dissociated from 3-4 week minals were studied h this report. Each result
Load more

Recommended publications
  • GABA Receptors
    D Reviews • BIOTREND Reviews • BIOTREND Reviews • BIOTREND Reviews • BIOTREND Reviews Review No.7 / 1-2011 GABA receptors Wolfgang Froestl , CNS & Chemistry Expert, AC Immune SA, PSE Building B - EPFL, CH-1015 Lausanne, Phone: +41 21 693 91 43, FAX: +41 21 693 91 20, E-mail: [email protected] GABA Activation of the GABA A receptor leads to an influx of chloride GABA ( -aminobutyric acid; Figure 1) is the most important and ions and to a hyperpolarization of the membrane. 16 subunits with γ most abundant inhibitory neurotransmitter in the mammalian molecular weights between 50 and 65 kD have been identified brain 1,2 , where it was first discovered in 1950 3-5 . It is a small achiral so far, 6 subunits, 3 subunits, 3 subunits, and the , , α β γ δ ε θ molecule with molecular weight of 103 g/mol and high water solu - and subunits 8,9 . π bility. At 25°C one gram of water can dissolve 1.3 grams of GABA. 2 Such a hydrophilic molecule (log P = -2.13, PSA = 63.3 Å ) cannot In the meantime all GABA A receptor binding sites have been eluci - cross the blood brain barrier. It is produced in the brain by decarb- dated in great detail. The GABA site is located at the interface oxylation of L-glutamic acid by the enzyme glutamic acid decarb- between and subunits. Benzodiazepines interact with subunit α β oxylase (GAD, EC 4.1.1.15). It is a neutral amino acid with pK = combinations ( ) ( ) , which is the most abundant combi - 1 α1 2 β2 2 γ2 4.23 and pK = 10.43.
    [Show full text]
  • A Review of Glutamate Receptors I: Current Understanding of Their Biology
    J Toxicol Pathol 2008; 21: 25–51 Review A Review of Glutamate Receptors I: Current Understanding of Their Biology Colin G. Rousseaux1 1Department of Pathology and Laboratory Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada Abstract: Seventy years ago it was discovered that glutamate is abundant in the brain and that it plays a central role in brain metabolism. However, it took the scientific community a long time to realize that glutamate also acts as a neurotransmitter. Glutamate is an amino acid and brain tissue contains as much as 5 – 15 mM glutamate per kg depending on the region, which is more than of any other amino acid. The main motivation for the ongoing research on glutamate is due to the role of glutamate in the signal transduction in the nervous systems of apparently all complex living organisms, including man. Glutamate is considered to be the major mediator of excitatory signals in the mammalian central nervous system and is involved in most aspects of normal brain function including cognition, memory and learning. In this review, the basic biology of the excitatory amino acids glutamate, glutamate receptors, GABA, and glycine will first be explored. In the second part of this review, the known pathophysiology and pathology will be described. (J Toxicol Pathol 2008; 21: 25–51) Key words: glutamate, glycine, GABA, glutamate receptors, ionotropic, metabotropic, NMDA, AMPA, review Introduction and Overview glycine), peptides (vasopressin, somatostatin, neurotensin, etc.), and monoamines (norepinephrine, dopamine and In the first decades of the 20th century, research into the serotonin) plus acetylcholine. chemical mediation of the “autonomous” (autonomic) Glutamatergic synaptic transmission in the mammalian nervous system (ANS) was an area that received much central nervous system (CNS) was slowly established over a research activity.
    [Show full text]
  • Calcium-Engaged Mechanisms of Nongenomic Action of Neurosteroids
    Calcium-engaged Mechanisms of Nongenomic Action of Neurosteroids The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters Citation Rebas, Elzbieta, Tomasz Radzik, Tomasz Boczek, and Ludmila Zylinska. 2017. “Calcium-engaged Mechanisms of Nongenomic Action of Neurosteroids.” Current Neuropharmacology 15 (8): 1174-1191. doi:10.2174/1570159X15666170329091935. http:// dx.doi.org/10.2174/1570159X15666170329091935. Published Version doi:10.2174/1570159X15666170329091935 Citable link http://nrs.harvard.edu/urn-3:HUL.InstRepos:37160234 Terms of Use This article was downloaded from Harvard University’s DASH repository, and is made available under the terms and conditions applicable to Other Posted Material, as set forth at http:// nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of- use#LAA 1174 Send Orders for Reprints to [email protected] Current Neuropharmacology, 2017, 15, 1174-1191 REVIEW ARTICLE ISSN: 1570-159X eISSN: 1875-6190 Impact Factor: 3.365 Calcium-engaged Mechanisms of Nongenomic Action of Neurosteroids BENTHAM SCIENCE Elzbieta Rebas1, Tomasz Radzik1, Tomasz Boczek1,2 and Ludmila Zylinska1,* 1Department of Molecular Neurochemistry, Faculty of Health Sciences, Medical University of Lodz, Poland; 2Boston Children’s Hospital and Harvard Medical School, Boston, USA Abstract: Background: Neurosteroids form the unique group because of their dual mechanism of action. Classically, they bind to specific intracellular and/or nuclear receptors, and next modify genes transcription. Another mode of action is linked with the rapid effects induced at the plasma membrane level within seconds or milliseconds. The key molecules in neurotransmission are calcium ions, thereby we focus on the recent advances in understanding of complex signaling crosstalk between action of neurosteroids and calcium-engaged events.
    [Show full text]
  • Product Update Price List Winter 2014 / Spring 2015 (£)
    Product update Price list winter 2014 / Spring 2015 (£) Say to affordable and trusted life science tools! • Agonists & antagonists • Fluorescent tools • Dyes & stains • Activators & inhibitors • Peptides & proteins • Antibodies hellobio•com Contents G protein coupled receptors 3 Glutamate 3 Group I (mGlu1, mGlu5) receptors 3 Group II (mGlu2, mGlu3) receptors 3 Group I & II receptors 3 Group III (mGlu4, mGlu6, mGlu7, mGlu8) receptors 4 mGlu – non-selective 4 GABAB 4 Adrenoceptors 4 Other receptors 5 Ligand Gated ion channels 5 Ionotropic glutamate receptors 5 NMDA 5 AMPA 6 Kainate 7 Glutamate – non-selective 7 GABAA 7 Voltage-gated ion channels 8 Calcium Channels 8 Potassium Channels 9 Sodium Channels 10 TRP 11 Other Ion channels 12 Transporters 12 GABA 12 Glutamate 12 Other 12 Enzymes 13 Kinase 13 Phosphatase 14 Hydrolase 14 Synthase 14 Other 14 Signaling pathways & processes 15 Proteins 15 Dyes & stains 15 G protein coupled receptors Cat no. Product name Overview Purity Pack sizes and prices Glutamate: Group I (mGlu1, mGlu5) receptors Agonists & activators HB0048 (S)-3-Hydroxyphenylglycine mGlu1 agonist >99% 10mg £112 50mg £447 HB0193 CHPG Sodium salt Water soluble, selective mGlu5 agonist >99% 10mg £59 50mg £237 HB0026 (R,S)-3,5-DHPG Selective mGlu1 / mGlu5 agonist >99% 10mg £70 50mg £282 HB0045 (S)-3,5-DHPG Selective group I mGlu receptor agonist >98% 1mg £42 5mg £83 10mg £124 HB0589 S-Sulfo-L-cysteine sodium salt mGlu1α / mGlu5a agonist 10mg £95 50mg £381 Antagonists HB0049 (S)-4-Carboxyphenylglycine Competitive, selective group 1
    [Show full text]
  • At the Gabaa Receptor
    THE EFFECTS OF CHRONIC ETHANOL INTAKE ON THE ALLOSTERIC INTERACTION BE T WEEN GABA AND BENZODIAZEPINE AT THE GABAA RECEPTOR THESIS Presented to the Graduate Council of the University of North Texas in Partial Fulfillment of the Requirements For the Degree of MASTER OF SCIENCE By Jianping Chen, B.S., M.S. Denton, Texas May, 1992 Chen, Jianping, The Effects of Chronic Ethanol Intake on the Allsteric Interaction Between GABA and BenzodiazeDine at the GABAA Receptor. Master of Science (Biomedical Sciences/Pharmacology), May, 1992, 133 pp., 4 tables, 3.0 figures, references, 103 titles. This study examined the effects of chronic ethanol intake on the density, affinity, and allosteric modulation of rat brain GABAA receptor subtypes. In the presence of GABA, the apparent affinity for the benzodiazepine agonist flunitrazepam was increased and for the inverse agonist R015-4513 was decreased. No alteration in the capacity of GABA to modulate flunitrazepam and R015-4513 binding was observed in membranes prepared from cortex, hippocampus or cerebellum following chronic ethanol intake or withdrawal. The results also demonstrate two different binding sites for [3H]RO 15-4513 in rat cerebellum that differ in their affinities for diazepam. Chronic ethanol treatment and withdrawal did not significantly change the apparent affinity or density of these two receptor subtypes. ACKNOWLEDGEMENT I would like to express my sincere thanks to my major professor, Dr. Michael W. Martin. .I deeply appreciate his guidance and direction which initiated this study, and his kindness in sharing his laboratory facilities with me. His suggestions, patience, encouragement and support in the laboratory have contributed significantly to my understanding of the receptor mechanism of drug action.
    [Show full text]
  • Neuroscience Products
    Neuroscience Products CATALOG CATALOG NUMBER U.S. $ NUMBER U.S. $ -A- 3-(N-ACETYLAMINO)-5-(N-DECYL-N- 1 mg 27.50 159549 METHYLAMINO)BENZYL ALCOHOL 5 mg 89.40 o A23187 0-5 C [103955-90-4] (ADMB) See: Antibiotic A23187 A Protein Kinase C activator. Ref.: Proc. Nat. Acad. Sci. USA, 83, 4214 AA-861 20 mg 72.70 (1986). 159061 Purity: 95% 100 mg 326.40 C20H34N2O2 MW 334.5 0oC Orally active, specific and potent inhibitor of 5-lipoxygenase. N-ACETYL-ASP-GLU 25 mg 45.00 153036 [3106-85-2] 100 mg 156.00 Ref.: 1. Yoshimoto, T., et.al., Biochim. o Biophys. Acta, 713, 470 (1982). 2. Ashida, -20-0 C An endogenous neuropeptide with high 250 mg 303.65 Y., et.al., Prostaglandins, 26, 955 (1983). 3. affinity for a brain "Glutamate" receptor. Ancill, R.J., et.al., J. Int. Med. Res., 18, 75 Ref: Zaczek, R., et al., Proc. Natl. Acad. (1990). Sci. (USA), 80, 1116 (1983). C21H26O3 MW 326.4 C11H16N2O8 MW 304.3 ABL PROTEIN TYROSINE KINASE 250 U 47.25 N-ACETYL-2-BENZYLTRYPTAMINE 195876 (v-abl) 1 KU 162.75 See: Luzindole -70oC Recombinant Expressed in E. coli ACETYL-DL-CARNITINE 250 mg 60.00 A truncated form of the v-abl protein 154690 [2504-11-2] 1 g 214.00 tyrosine kinase which contains the 0oC Hydrochloride minimum region needed for kinase activity Crystalline and fibroblast transformation. Suppresses C9H17NO4 • HCl MW 239.7 apoptosis and induces resistance to anti-cancer compounds. O-ACETYL-L-CARNITINE CHLORIDE 500 mg 11.45 Activity: 100 KU/ml 159062 [5080-50-2] 1 g 20.65 Unit Definition: one unit is the amount of 0-5oC (R-(-)-2-Acetyloxy-3-carboxy-N,N,N-trimethyl 5 g 97.45 enzyme which catalyzes the transfer of 1 -1-propanaminium chloride) pmol of phosphate to EAIYAAPFAKKK per Purity: >88% minute at 30°C, pH 7.5.
    [Show full text]
  • AMINO ACID NEUROTRANSMISSION DURING CHEMICALLY-INDUCED EPILEPTOGENIC ACTIVITY in the RAT CEREBRAL CORTEX. a Thesis Submitted To
    AMINO ACID NEUROTRANSMISSION DURING CHEMICALLY-INDUCED EPILEPTOGENIC ACTIVITY IN THE RAT CEREBRAL CORTEX. A thesis submitted to the University of London for the degree of Doctor of Philosophy by Farzin ZIA GHARIB Department of Pharmacology, University College London Gower Street London WC1E 6BT 1 ProQuest Number: 10609198 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a com plete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. uest ProQuest 10609198 Published by ProQuest LLC(2017). Copyright of the Dissertation is held by the Author. All rights reserved. This work is protected against unauthorized copying under Title 17, United States C ode Microform Edition © ProQuest LLC. ProQuest LLC. 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106- 1346 IN THE NAME OF GOD, THE COMPASSIONATE, THE MERCIFUL This thesis is dedicated to my dear parents, for their unwavering support and encouragement, and the rest of my family, Farzaneh, Farzad and Nader 2 ABSTRACT This project was undertaken firstly to establish a relationship between chemically-induced epileptogenic activity and the release of amino acid neurotransmitters and secondly to try to compare the enhancement of r-aminobutyric acid (GABA)-mediated inhibition with the blockade of excitatory amino acid receptors in the control of epileptogenic activity in rat cerebral cortex. Using cortical cups incorporating platinum electrodes, it was possible to monitor epileptogenic activity in the electroencephalogram (EEG), quantified using a specially designed voltage integrator, at the same time as studying the release of endogenous amino acids.
    [Show full text]
  • Amino Acids and N-Acetyl-Aspartyl-Glutamate As Neurotransmitter Candidates in the Monkey Retinogeniculate Pathways
    City University of New York (CUNY) CUNY Academic Works All Dissertations, Theses, and Capstone Projects Dissertations, Theses, and Capstone Projects 1989 Amino Acids and N-acetyl-aspartyl-glutamate as Neurotransmitter Candidates in the Monkey Retinogeniculate Pathways Ricardo A. Molinar-Rode Graduate Center, City University of New York How does access to this work benefit ou?y Let us know! More information about this work at: https://academicworks.cuny.edu/gc_etds/1641 Discover additional works at: https://academicworks.cuny.edu This work is made publicly available by the City University of New York (CUNY). Contact: [email protected] INFORMATION TO USERS The most advanced technology has been used to photo­ graph and reproduce this manuscript from the microfilm master. UMI films the text directly from the original or copy submitted. Thus, some thesis and dissertation copies are in typewriter face, while others may be from any type of computer printer. The quality of this reproduction is dependent upon the quality of the copy submitted. Broken or indistinct print, colored or poor quality illustrations and photographs, print bleedthrough, substandard margins, and improper alignment can adversely affect reproduction. In the unlikely event that the author did not send UMI a complete manuscript and there are missing pages, these will be noted. Also, if unauthorized copyright material had to be removed, a note will indicate the deletion. Oversize materials (e.g., maps, drawings, charts) are re­ produced by sectioning the original, beginning at the upper left-hand corner and continuing from left to right in equal sections with small overlaps. Each original is also photographed in one exposure and is included in reduced form at the back of the book.
    [Show full text]
  • Release-Regulating Autoreceptors of the GABAB-Type in Human Cerebral Cortex
    Br. J. Pharmacol. (1989), 96, 341-346 Release-regulating autoreceptors of the GABAB-type in human cerebral cortex Giambattista Bonanno *Paolo Cavazzani, *Gian Carlo Andrioli, Daniela Asaro, Graziella Pellegrini & tMaurizio Raiteri Istituto di Farmacologia e Farmacognosia, Universita degli Studi di Genova, Viale Cembrano 4, 16148 Genova, Italy & *Divisione di Neurochirurgia, Ospedali Galliera, Via A. Volta 8, 16128 Genova, Italy 1 The depolarization-evoked release of y-aminobutyric acid (GABA) and its modulation mediated by autoreceptors were investigated in superfused synaptosomes prepared from fresh human cerebral cortex. 2 The release of [3H]-GABA provoked by 15 mmK+ from human cortex nerve endings was almost totally (85%) calcium-dependent. 3 In the presence of the GABA uptake inhibitor SK&F 89976A (N-4,4-diphenyl-3-butenyl)-nipe- cotic acid), added to prevent carrier-mediated homoexchange, GABA (1-10 pM) decreased in a concentration-dependent manner the K+-evoked release of [3H]-GABA. The effect of GABA was mimicked by the GABAB receptor agonist (-)-baclofen (1-100 pM) but not by the GABAA receptor agonist muscimol (1-100 uM). Moreover, the GABA-induced inhibition of [3H]-GABA release was not affected by two GABAA receptor antagonists, bicuculline or SR 95531 (2-(3'-carbethoxy-2'- propenyl)-3-amino-6-paramethoxy-phenyl-pyridazinium bromide). 4 (-)-Baclofen also inhibited the depolarization-evoked release of endogenous GABA from human cortical synaptosomes. 5 It is concluded that GABA autoreceptors regulating the release of both newly taken up and endogenous GABA are present in human brain and appear to belong to the GABAB subtype. Introduction Studies on the laboratory animal have shown that GABA in the rat brain of the GABAB receptor autoregulation of transmitter release mediated by subtype (Anderson & Mitchell, 1985; Pittaluga et al., receptors sited on the releasing terminals 1987; Waldmeier et al., 1988).
    [Show full text]
  • Receptor-Mediated Inhibition of the N-Methyl-O-Aspartate Component of Synaptic Transmission in the Rat Hippocampus
    The Journal of Neuroscience, January 1991, 17(l): 203-209 GABA,-Receptor-Mediated Inhibition of the N-Methyl-o-Aspartate Component of Synaptic Transmission in the Rat Hippocampus Richard A. Morrisett,1-5 David D. Mott,2 Darrell V. Lewis,3 H. Scott Swartzwelder,i,4.5 and Wilkie A. Wilson1-*v5 Departments of ‘Medicine (Neurology), *Pharmacology, 3Pediatrics (Neurology) and Neurobiology, and 4Psychology, Duke University Medical Center, Durham, North Carolina 27710. and 5Neurology Research Laboratory, Veterans Administration Medical Center, Durham, North Carolina 27705 GABA receptor regulation of NMDA-receptor-mediated syn- operated channelsare regulated in a voltage-dependentmanner aptic responses was studied in area CA, of the rat hippocam- by Mg2+ (Mayer and Westbrook, 1984; Nowak et al., 1984; pus using extracellular and intracellular recording tech- Herron et al., 1986). Becauseof the development of specific niques. Picrotoxin (PTX) was used to suppress GABA, non-NMDA receptor antagonists such as 6,7-dinitroquinoxa- inhibition and 6,7-dinitroquinoxaline-2,3-dione (DNQX) was line-2,3-dione (DNQX; Drejer and Honor& 1988) the dem- used to suppress non-NMDA receptor-mediated responses. onstration of NMDA-receptor-mediated synaptic potentials has In this manner, we were able to avoid the complicating fac- been facilitated (Blake et al., 1988; Andreasen et al., 1989; Da- tors caused by potentials induced by other excitatory and vies and Collingridge, 1989; Iambert and Jones, 1989). When, inhibitory amino acid receptors. Under these conditions, large in the presenceof DNQX, synaptic inhibition is reduced or NMDA-receptor-mediated EPSPs were observed. When blocked, one can record large depolarizing responsesto NMDA paired stimuli were given at interstimulus intervals from 100 receptor activation (Andreasen et al., 1989; Davies and Collin- to 400 msec, powerful inhibition of the second response was gridge, 1989; Lambert and Jones, 1989; Morrisett et al., 1990b).
    [Show full text]
  • GABA Receptors
    Tocris Scientific ReviewReview SeriesSeries Tocri-lu-2945 GABA Receptors Ian L. Martin, Norman G. Bowery Historical Perspective and Susan M.J. Dunn GABA is the major inhibitory amino acid transmitter of the Ian Martin is Professor of Pharmacology in the School of Life and mammalian central nervous system (CNS). Essentially all neurons Health Sciences, Aston University, Birmingham, UK. Norman in the brain respond to GABA and perhaps 20% use it as their 1 Bowery is Emeritus Professor of Pharmacology, University of primary transmitter. Early electrophysiological studies, carried Birmingham, UK. Susan Dunn is Professor and Chair at the out using iontophoretic application of GABA to CNS neuronal Department of Pharmacology, Faculty of Medicine and Dentistry, preparations, showed it to produce inhibitory hyperpolarizing 2 University of Alberta, Canada. All three authors share common responses that were blocked competitively by the alkaloid 3 interests in GABAergic transmission. E-mail: sdunn@pmcol. bicuculline. However, in the late 1970s, Bowery and his ualberta.ca colleagues, who were attempting to identify GABA receptors on peripheral nerve terminals, noted that GABA application reduced the evoked release of noradrenalin in the rat heart and that this Contents effect was not blocked by bicuculline. This action of GABA was Introduction ............................................................................................. 1 mimicked, however, by baclofen (Figure 1), a compound that was unable to produce rapid hyperpolarizing responses
    [Show full text]
  • Effect of Intracerebroventricular Injection of GABA Receptors
    Iranian Journal of Basic Medical Sciences ijbms.mums.ac.ir Effect of intracerebroventricular injection of GABA receptors antagonists on morphine-induced changes in GABA and GLU transmission within the mPFC: an in vivo microdialysis study Effat Ramshini 1, Hojjatallah Alaei 1*, Parham Reisi 1, Naser Naghdi 2, Hossein Afrozi 3, Samaneh Alaei 1, Maryam Alehashem 4 5 1 Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran 2 Department of Physiology, Pasteur Institute, Shahrzad of Iran, Tehran, Eftekharvaghefi Iran 3 Drug Research Center of Daropakhsh, Tehran, Iran 4 Tracheal Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran 5 Department of Physiology, Kerman University of Medical Sciences, Kerman, Iran A R T I C L E I N F O A B S T R A C T Article type: Objective(s): Many studies have focused on ventral tegmental area than of other mesocorticolimbic Original article areas, and implicated a key role for the medial prefrontal cortex (mPFC) in the development of addictive behaviors. So far, the role of gamma-aminobutyric acid (GABA) receptors in the Article history: discriminative properties of morphine has received little attention and few studies evaluated the role Received: Dec 22, 2017 Accepted: Sep 22, 2018 of these receptors in drug dependence. Hence, we investigated the role of this receptor on morphine- induced GABA/ glutamate (GLU) changes in the mPFC following morphine administration using in Keywords: vivo microdialysis. Addiction, Materials and Methods: In this study, 60 rats weighing 270-300 g were divided into six groups.
    [Show full text]