Biomaterial Database

Steroid modulation of the GABAA receptor complex: electrophysiological studies. 1990

J J Lambert, and J A Peters, and N C Sturgess, and T G Hales

Department of Pharmacology & Clinical Pharmacology, Ninewells Hospital & Medical School, Dundee University, UK.

The effect of some endogenous and synthetic steroids on the operation of inhibitory and excitatory amino acid neurotransmitter receptors was examined. Anaesthetic pregnane steroids (e.g. alphaxalone, 5 alpha-pregnan-3 alpha-ol-20-one, 5 alpha-pregnane-3 alpha,21-diol-20-one) potentiated GABAA receptor-mediated whole-cell currents recorded from bovine chromaffin cells. The threshold concentration for enhancement was 10-30 nM. Potentiation was stereoselective and was mediated by a steroid-induced prolongation of the burst duration of the GABA-activated channel. Additionally, the pregnane steroids directly activated the GABAA receptor. Both the potentiation and activation appear to be mediated through a site(s) distinct from the well-known barbiturate and benzodiazepine allosteric sites of the GABAA receptor. Intracellularly applied alphaxalone and 5 beta-pregnan-3 alpha-ol-20-one had no discernible effects on the GABAA receptor, suggesting that the steroid binding site can only be accessed extracellularly. Unlike behaviourally depressant barbiturates, which modulate GABAA receptor function in a manner similar to that of the pregnane steroids, alphaxalone and 5 beta-pregnan-3 alpha-ol-20-one show striking pharmacological selectivity. Voltage-clamp recordings from rat central neurons in culture indicate that pentobarbitone exerts its potentiating and GABA-mimetic effects over a range of concentrations which also depress currents mediated by glutamate receptor subtypes. In contrast, alphaxalone and several endogenous steroids greatly enhance responses to GABA, but have no direct effect on glutamate receptors. Such pharmacological selectivity, coupled with appropriate stereoselectivity of action, suggests that the GABAA receptor mediates some of the behavioural effects of synthetic and endogenous pregnane steroids.

UI	MeSH Term	Description	Entries
D008565	Membrane Proteins	Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.	Cell Membrane Protein,Cell Membrane Proteins,Cell Surface Protein,Cell Surface Proteins,Integral Membrane Proteins,Membrane-Associated Protein,Surface Protein,Surface Proteins,Integral Membrane Protein,Membrane Protein,Membrane-Associated Proteins,Membrane Associated Protein,Membrane Associated Proteins,Membrane Protein, Cell,Membrane Protein, Integral,Membrane Proteins, Integral,Protein, Cell Membrane,Protein, Cell Surface,Protein, Integral Membrane,Protein, Membrane,Protein, Membrane-Associated,Protein, Surface,Proteins, Cell Membrane,Proteins, Cell Surface,Proteins, Integral Membrane,Proteins, Membrane,Proteins, Membrane-Associated,Proteins, Surface,Surface Protein, Cell
D011277	Pregnanediones	Pregnane derivatives in which two side-chain methyl groups or two methylene groups in the ring skeleton (or a combination thereof) have been oxidized to keto groups.	Diketopregnanes,Dioxopregnanes
D011280	Pregnanolone	A pregnane found in the urine of pregnant women and sows. It has anesthetic, hypnotic, and sedative properties.	Eltanolone,3 alpha, 5 beta-Tetrahydroprogesterone,3 alpha-Hydroxy-5 alpha-pregnan-20-one,3 alpha-Hydroxy-5 beta-pregnan-20-one,3-Hydroxypregnan-20-one,3beta-Hydroxy-5alpha-pregnan-20-one,Allopregnan-3 beta-ol-20-one,Allopregnanolone,Epipregnanolone,Pregnan-3alpha-ol-20-one,Pregnanolone, (3alpha)-isomer,Pregnanolone, (3alpha, 5beta, 17-alpha)-isomer,Pregnanolone, (3alpha,5alpha)-isomer,Pregnanolone, (3alpha,5beta)-isomer,Pregnanolone, (3beta)-isomer,Pregnanolone, (3beta, 5alpha)-isomer,Pregnanolone, (3beta, 5alpha, 17alpha)-isomer,Pregnanolone, (3beta, 5alpha, 8alpha, 17beta)-isomer,Pregnanolone, (3beta, 5beta)-isomer,Pregnanolone, (3beta, 5beta, 17alpha)-isomer,Pregnanolone, (3beta, 5beta,14beta)-isomer,Pregnanolone, (5alpha)-isomer,Sepranolone,3 Hydroxypregnan 20 one,3 alpha Hydroxy 5 alpha pregnan 20 one,3 alpha Hydroxy 5 beta pregnan 20 one,3 alpha, 5 beta Tetrahydroprogesterone,3beta Hydroxy 5alpha pregnan 20 one,Allopregnan 3 beta ol 20 one,Pregnan 3alpha ol 20 one,alpha-Hydroxy-5 alpha-pregnan-20-one, 3,alpha-Hydroxy-5 beta-pregnan-20-one, 3,alpha-pregnan-20-one, 3 alpha-Hydroxy-5,beta-ol-20-one, Allopregnan-3,beta-pregnan-20-one, 3 alpha-Hydroxy-5
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
D002417	Cattle	Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.	Beef Cow,Bos grunniens,Bos indicus,Bos indicus Cattle,Bos taurus,Cow,Cow, Domestic,Dairy Cow,Holstein Cow,Indicine Cattle,Taurine Cattle,Taurus Cattle,Yak,Zebu,Beef Cows,Bos indicus Cattles,Cattle, Bos indicus,Cattle, Indicine,Cattle, Taurine,Cattle, Taurus,Cattles, Bos indicus,Cattles, Indicine,Cattles, Taurine,Cattles, Taurus,Cow, Beef,Cow, Dairy,Cow, Holstein,Cows,Dairy Cows,Domestic Cow,Domestic Cows,Indicine Cattles,Taurine Cattles,Taurus Cattles,Yaks,Zebus
D002838	Chromaffin System	The cells of the body which stain with chromium salts. They occur along the sympathetic nerves, in the adrenal gland, and in various other organs.	Argentaffin System,Argentaffin Systems,Chromaffin Systems,System, Argentaffin,System, Chromaffin,Systems, Argentaffin,Systems, Chromaffin
D003900	Desoxycorticosterone	A steroid metabolite that is the 11-deoxy derivative of CORTICOSTERONE and the 21-hydroxy derivative of PROGESTERONE	21-Hydroxyprogesterone,Cortexone,Deoxycorticosterone,Desoxycortone,11-Decorticosterone,21-Hydroxy-4-pregnene-3,20-dione,11 Decorticosterone,21 Hydroxy 4 pregnene 3,20 dione,21 Hydroxyprogesterone
D004594	Electrophysiology	The study of the generation and behavior of electrical charges in living organisms particularly the nervous system and the effects of electricity on living organisms.
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
D000777	Anesthetics	Agents capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general ANESTHESIA, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site.	Anesthetic,Anesthetic Agents,Anesthetic Drugs,Anesthetic Effect,Anesthetic Effects,Agents, Anesthetic,Drugs, Anesthetic,Effect, Anesthetic,Effects, Anesthetic