Biomaterial Database

Discrimination of post- and presynaptic GABAB receptor-mediated responses by tetrahydroaminoacridine in area CA3 of the rat hippocampus. 1993

N A Lambert, and W A Wilson

Department of Pharmacology, Duke University Medical Center, Durham, North Carolina.

1. The effects of the K+ channel blocker 9-amino-1,2,3,4-tetrahydroacridine (THA) on the actions of baclofen and gamma-aminobutyric acid (GABA) at post- and presynaptic GABAB receptors were studied with whole-cell voltage-clamp recording in area CA3 of rat hippocampal slices. 2. The effect of THA on postsynaptic GABAB receptor-mediated responses was studied in neurons perfused internally with potassium gluconate and guanosine triphosphate (GTP). At a holding potential of -70 mV, the GABAB receptor agonist (+/-)-baclofen (30 microM) induced an outward current and increased membrane conductance. In the presence of the excitatory amino acid receptor antagonists 6,7-dinitroquinoxaline-2,3-dione (DNQX) and (+/-)-2-amino-5-phosphonovalerate (APV), stimulation in stratum pyramidale or proximal stratum radiatum evoked GABAA receptor-mediated, fast monosynaptic inhibitory postsynaptic currents (IPSCs) and GABAB receptor-mediated, late monosynaptic IPSCs. THA (0.3 mM) blocked the baclofen-induced current and conductance increase and GABAB receptor-mediated IPSCs. 3. The effect of THA on presynaptic GABAB receptor-mediated responses was studied in neurons perfused internally with Cs+ and lidocaine N-ethyl bromide (QX-314), which blocked post-synaptic GABAB receptor-mediated responses. Stimulation in the presence of DNQX and APV evoked GABAA receptor-mediated IPSCs; when pairs of stimuli were delivered 200 ms apart the second IPSC was depressed. Baclofen reversibly depressed IPSCs, and partially occluded paired-pulse depression of IPSCs. The GABAB receptor antagonist CGP 35348 (0.5-1.0 mM) reversed baclofen-induced depression of IPSCs and partially blocked paired-pulse depression. Baclofen-induced and paired-pulse depression of IPSCs were not by affected by THA (0.3 mM). 4. Baclofen reversibly decreased the amplitude and frequency of spontaneous monosynaptic IPSCs (sIPSCs). Depression of sIPSCs by baclofen was unchanged by THA. 5. These results indicate that THA blocks the actions of baclofen and GABA at post- but not presynaptic GABAB receptors. We conclude that post- and presynaptic GABAB receptors in area CA3 of the rat hippocampus couple to different effector mechanisms; postsynaptic GABAB receptors activate THA-sensitive K+ channels, and presynaptic GABAB receptors decrease neurotransmitter release through a THA-insensitive mechanism.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D009943	Organophosphorus Compounds	Organic compounds that contain phosphorus as an integral part of the molecule. Included under this heading is broad array of synthetic compounds that are used as PESTICIDES and DRUGS.	Organophosphorus Compound,Organopyrophosphorus Compound,Organopyrophosphorus Compounds,Compound, Organophosphorus,Compound, Organopyrophosphorus,Compounds, Organophosphorus,Compounds, Organopyrophosphorus
D011810	Quinoxalines		Quinoxaline
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
D005071	Evoked Potentials	Electrical responses recorded from nerve, muscle, SENSORY RECEPTOR, or area of the CENTRAL NERVOUS SYSTEM following stimulation. They range from less than a microvolt to several microvolts. The evoked potential can be auditory (EVOKED POTENTIALS, AUDITORY), somatosensory (EVOKED POTENTIALS, SOMATOSENSORY), visual (EVOKED POTENTIALS, VISUAL), or motor (EVOKED POTENTIALS, MOTOR), or other modalities that have been reported.	Event Related Potential,Event-Related Potentials,Evoked Potential,N100 Evoked Potential,P50 Evoked Potential,N1 Wave,N100 Evoked Potentials,N2 Wave,N200 Evoked Potentials,N3 Wave,N300 Evoked Potentials,N4 Wave,N400 Evoked Potentials,P2 Wave,P200 Evoked Potentials,P50 Evoked Potentials,P50 Wave,P600 Evoked Potentials,Potentials, Event-Related,Event Related Potentials,Event-Related Potential,Evoked Potential, N100,Evoked Potential, N200,Evoked Potential, N300,Evoked Potential, N400,Evoked Potential, P200,Evoked Potential, P50,Evoked Potential, P600,Evoked Potentials, N100,Evoked Potentials, N200,Evoked Potentials, N300,Evoked Potentials, N400,Evoked Potentials, P200,Evoked Potentials, P50,Evoked Potentials, P600,N1 Waves,N2 Waves,N200 Evoked Potential,N3 Waves,N300 Evoked Potential,N4 Waves,N400 Evoked Potential,P2 Waves,P200 Evoked Potential,P50 Waves,P600 Evoked Potential,Potential, Event Related,Potential, Event-Related,Potential, Evoked,Potentials, Event Related,Potentials, Evoked,Potentials, N400 Evoked,Related Potential, Event,Related Potentials, Event,Wave, N1,Wave, N2,Wave, N3,Wave, N4,Wave, P2,Wave, P50,Waves, N1,Waves, N2,Waves, N3,Waves, N4,Waves, P2,Waves, P50
D006624	Hippocampus	A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation.	Ammon Horn,Cornu Ammonis,Hippocampal Formation,Subiculum,Ammon's Horn,Hippocampus Proper,Ammons Horn,Formation, Hippocampal,Formations, Hippocampal,Hippocampal Formations,Hippocampus Propers,Horn, Ammon,Horn, Ammon's,Proper, Hippocampus,Propers, Hippocampus,Subiculums
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001418	Baclofen	A GAMMA-AMINOBUTYRIC ACID derivative that is a specific agonist of GABA-B RECEPTORS. It is used in the treatment of MUSCLE SPASTICITY, especially that due to SPINAL CORD INJURIES. Its therapeutic effects result from actions at spinal and supraspinal sites, generally the reduction of excitatory transmission.	Baclophen,Chlorophenyl GABA,Apo-Baclofen,Atrofen,Ba-34,647,Ba-34647,Baclofen AWD,Baclofène-Irex,Baclospas,CIBA-34,647-BA,Clofen,Gen-Baclofen,Genpharm,Lebic,Lioresal,Liorésal,Nu-Baclo,PCP-GABA,PMS-Baclofen,beta-(Aminomethyl)-4-chlorobenzenepropanoic Acid,beta-(p-Chlorophenyl)-gamma-aminobutyric Acid,AWD, Baclofen,Apo Baclofen,ApoBaclofen,Ba34,647,Ba34647,Baclofène Irex,BaclofèneIrex,CIBA34,647BA,GABA, Chlorophenyl,Gen Baclofen,GenBaclofen,Nu Baclo,NuBaclo,PMS Baclofen,PMSBaclofen
D013569	Synapses	Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate via direct electrical coupling with ELECTRICAL SYNAPSES. Several other non-synaptic chemical or electric signal transmitting processes occur via extracellular mediated interactions.	Synapse
D013619	Tacrine	A cholinesterase inhibitor that crosses the blood-brain barrier. Tacrine has been used to counter the effects of muscle relaxants, as a respiratory stimulant, and in the treatment of Alzheimer's disease and other central nervous system disorders.	Tetrahydroaminoacridine,1,2,3,4-Tetrahydro-9-acridinamine,1,2,3,4-Tetrahydroaminoacridine,9-Amino-1,2,3,4-Tetrahydroacridine,Cognex,Romotal,THA,Tacrine Hydrochloride,Tenakrin