Antagonist inhibition of GABAA-mediated chloride uptake is atypical in nigrocollicular areas. 1993

J Peris
Dept. Pharmacodynamics, University of Florida Health Sciences Center, Gainesville 32610.

Marked regional differences in the mRNA levels for the different subunits of the GABAA receptor may result in functional differences throughout the brain. The effects of different GABAA agonists and antagonists on GABAA receptor function was measured using 36Cl- uptake in microsacs made from cerebellum (CB), superior colliculus (SC), substantia nigra (SN), inferior colliculus (IC) or cortex (CT) containing equal amounts of protein. GABA increased Cl- uptake in all regions in a dose-dependent and saturable manner but with markedly different efficacies across brain regions. Maximal GABA-stimulated uptake was 59 +/- 2 nmoles of Cl- per mg protein in CT, 25 +/- 5 in SC, 24 +/- 4 in CB, 16 +/- 1 in IC and 6.7 +/- 1.4 in SN. Muscimol increased Cl- uptake with greater potency than GABA but with similar efficacies in CT, CB, SC and SN; the efficacy of muscimol in IC was increased to 27.4 +/- 5. Picrotoxin inhibited maximal GABA-stimulated Cl- uptake in CB, SC and CT but did not decrease uptake in IC or SN. Bicuculline methiodide completely inhibited uptake in CB and CT, partially inhibited uptake in IC, and did not affect uptake in SC and SN. These data provide functional support for regional heterogeneity of the GABAA receptor/Cl- ionophore between nigrocollicular regions and CB and CT.

UI MeSH Term Description Entries
D007245 Inferior Colliculi The posterior pair of the quadrigeminal bodies which contain centers for auditory function. Colliculus, Inferior,Brachial Nucleus of the Inferior Colliculus,Caudal Colliculus,Colliculus Inferior,Inferior Colliculus,Posterior Colliculus,Colliculi, Inferior,Colliculus Inferiors,Colliculus, Caudal,Colliculus, Posterior,Inferior, Colliculus,Inferiors, Colliculus
D007476 Ionophores Chemical agents that increase the permeability of biological or artificial lipid membranes to specific ions. Most ionophores are relatively small organic molecules that act as mobile carriers within membranes or coalesce to form ion permeable channels across membranes. Many are antibiotics, and many act as uncoupling agents by short-circuiting the proton gradient across mitochondrial membranes. Ionophore
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008297 Male Males
D010852 Picrotoxin A mixture of PICROTOXININ and PICROTIN that is a noncompetitive antagonist at GABA-A receptors acting as a convulsant. Picrotoxin blocks the GAMMA-AMINOBUTYRIC ACID-activated chloride ionophore. Although it is most often used as a research tool, it has been used as a CNS stimulant and an antidote in poisoning by CNS depressants, especially the barbiturates. 3,6-Methano-8H-1,5,7-trioxacyclopenta(ij)cycloprop(a)azulene-4,8(3H)-dione, hexahydro-2a-hydroxy-9-(1-hydroxy-1-methylethyl)-8b-methyl-, (1aR-(1aalpha,2abeta,3beta,6beta,6abeta,8aS*,8bbeta,9S*))-, compd. with (1aR-(1aalpha,2abeta,3beta,6beta,6abeta,8,Cocculin
D011868 Radioisotopes Isotopes that exhibit radioactivity and undergo radioactive decay. (From Grant & Hackh's Chemical Dictionary, 5th ed & McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) Daughter Isotope,Daughter Nuclide,Radioactive Isotope,Radioactive Isotopes,Radiogenic Isotope,Radioisotope,Radionuclide,Radionuclides,Daughter Nuclides,Daugter Isotopes,Radiogenic Isotopes,Isotope, Daughter,Isotope, Radioactive,Isotope, Radiogenic,Isotopes, Daugter,Isotopes, Radioactive,Isotopes, Radiogenic,Nuclide, Daughter,Nuclides, Daughter
D011963 Receptors, GABA-A Cell surface proteins which bind GAMMA-AMINOBUTYRIC ACID and contain an integral membrane chloride channel. Each receptor is assembled as a pentamer from a pool of at least 19 different possible subunits. The receptors belong to a superfamily that share a common CYSTEINE loop. Benzodiazepine-Gaba Receptors,GABA-A Receptors,Receptors, Benzodiazepine,Receptors, Benzodiazepine-GABA,Receptors, Diazepam,Receptors, GABA-Benzodiazepine,Receptors, Muscimol,Benzodiazepine Receptor,Benzodiazepine Receptors,Benzodiazepine-GABA Receptor,Diazepam Receptor,Diazepam Receptors,GABA(A) Receptor,GABA-A Receptor,GABA-A Receptor alpha Subunit,GABA-A Receptor beta Subunit,GABA-A Receptor delta Subunit,GABA-A Receptor epsilon Subunit,GABA-A Receptor gamma Subunit,GABA-A Receptor rho Subunit,GABA-Benzodiazepine Receptor,GABA-Benzodiazepine Receptors,Muscimol Receptor,Muscimol Receptors,delta Subunit, GABA-A Receptor,epsilon Subunit, GABA-A Receptor,gamma-Aminobutyric Acid Subtype A Receptors,Benzodiazepine GABA Receptor,Benzodiazepine Gaba Receptors,GABA A Receptor,GABA A Receptor alpha Subunit,GABA A Receptor beta Subunit,GABA A Receptor delta Subunit,GABA A Receptor epsilon Subunit,GABA A Receptor gamma Subunit,GABA A Receptor rho Subunit,GABA A Receptors,GABA Benzodiazepine Receptor,GABA Benzodiazepine Receptors,Receptor, Benzodiazepine,Receptor, Benzodiazepine-GABA,Receptor, Diazepam,Receptor, GABA-A,Receptor, GABA-Benzodiazepine,Receptor, Muscimol,Receptors, Benzodiazepine GABA,Receptors, GABA A,Receptors, GABA Benzodiazepine,delta Subunit, GABA A Receptor,epsilon Subunit, GABA A Receptor,gamma Aminobutyric Acid Subtype A Receptors
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D002712 Chlorides Inorganic compounds derived from hydrochloric acid that contain the Cl- ion. Chloride,Chloride Ion Level,Ion Level, Chloride,Level, Chloride Ion
D002713 Chlorine An element with atomic symbol Cl, atomic number 17, and atomic weight 35, and member of the halogen family. Chlorine Gas,Chlorine-35,Cl2 Gas,Chlorine 35,Gas, Chlorine,Gas, Cl2
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