Các Metabolite Hormone Steroid Là Những Chất Điều Biến Tương Tự Barbiturate Của Receptor GABA

American Association for the Advancement of Science (AAAS) - Tập 232 Số 4753 - Trang 1004-1007 - 1986
Monika Majewska1, Neil L. Harrison2, Rochelle D. Schwartz1, Jeffery L. Barker2, Steven M. Paul1
1Sections on Molecular Pharmacology and Preclinical Studies, Clinical Neuroscience Branch, National Institute of Mental Health, Bethesda, MD 20892.
2Laboratory of Neurophysiology, National Institute of Neurological and Communicative Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.

Tóm tắt

Hai loại metabolite của hormone steroid progesterone và deoxycorticosterone, 3α-hydroxy-5α-dihydroprogesterone và 3α,5α-tetrahydrodeoxycorticosterone, là những ligand kiểu barbiturate mạnh đối với phức hợp kênh ion chloride của receptor γ-aminobutyric acid (GABA). Ở nồng độ từ 10 -7 đến 10 -5 M , cả hai steroid này đã ức chế sự gắn kết của chất gây co giật t-butylbicyclophosphorothionate vào phức hợp receptor GABA và tăng cường sự gắn kết của benzodiazepine flunitrazepam; chúng cũng kích thích sự hấp thụ chloride (theo dõi thông qua việc hấp thụ 36 Cl - ) vào các túi não izolated, và tăng cường các tác động ức chế của GABA trong các tế bào thần kinh vỏ não và tủy sống của chuột cưng. Dữ liệu này có thể giải thích khả năng của một số hormone steroid để nhanh chóng thay đổi độ nhạy cảm thần kinh và có thể cung cấp một cơ chế cho các tác động gây mê và gây ngủ của các hormone steroid gây mê tự nhiên và tổng hợp.

Từ khóa


Tài liệu tham khảo

ADAMS, P.R., ADVANCES IN PHYSIOLOGICAL SCIENCES 4: 135 (1981).

AKAIKE, N, GAMMA-AMINOBUTYRIC-ACID-GATED AND PENTOBARBITONE-GATED CHLORIDE CURRENTS IN INTERNALLY PERFUSED FROG SENSORY NEURONS, JOURNAL OF PHYSIOLOGY-LONDON 360: 367 (1985).

ATKINSON, R.M., ACTION OF SOME STEROIDS ON CENTRAL NERVOUS SYSTEM OF MOUSE .2. PHARMACOLOGY, JOURNAL OF MEDICINAL CHEMISTRY 8: 426 (1965).

BARKER, J.L., PENTOBARBITAL PHARMACOLOGY OF MAMMALIAN CENTRAL NEURONS GROWN IN TISSUE-CULTURE, JOURNAL OF PHYSIOLOGY-LONDON 280: 355 (1978).

BAULIEU, E.E., STEROID HORMONE REGU: 3 (1980).

CHILD, K.J., PHARMACOLOGICAL PROPERTIES IN ANIMALS OF CT1341 - NEW STEROID ANAESTHETIC AGENT, BRITISH JOURNAL OF ANAESTHESIA 43: 2 (1971).

COSTA, E, NEW CONCEPTS ON MECHANISM OF ACTION OF BENZODIAZEPINES, LIFE SCIENCES 17: 167 (1975).

DUBROVSKY, B, EFFECTS OF DEOXYCORTICOSTERONE AND ITS RING A-REDUCED DERIVATIVES ON THE NERVOUS-SYSTEM, EXPERIMENTAL NEUROLOGY 78: 728 (1982).

ENNA, S.J., BIOCHEMICAL AND ELECTRO-PHYSIOLOGICAL CHARACTERISTICS OF MAMMALIAN GABA RECEPTORS, INTERNATIONAL REVIEW OF NEUROBIOLOGY 24: 181 (1983).

FELDMAN, S, INTEGRATIVE NEUROHUM: 173 (1983).

FENWICK, E.M., A PATCH-CLAMP STUDY OF BOVINE CHROMAFFIN CELLS AND OF THEIR SENSITIVITY TO ACETYLCHOLINE, JOURNAL OF PHYSIOLOGY-LONDON 331: 577 (1982).

GYERMEK, L, STEROID ANESTHETICS, ANESTHESIOLOGY 42: 331 (1975).

HAEFELY, W, ANXIOLYTICS NEUROCHE: 113 (1983).

10.1007/BF00656997

HARRISON, N.L., MODULATION OF THE GABA RECEPTOR COMPLEX BY A STEROID ANESTHETIC, BRAIN RESEARCH 323: 287 (1984).

Harrison N. L. unpublished observations.

HARRISON, N.L., SOCIETY FOR NEUROSCIENCE. ABSTRACTS 15: 81 (1985).

HOLZBAUER, M, J PHYSL LONDON 210: 123 (1970).

HOLZBAUER, M, PHYSIOLOGICAL ASPECTS OF STEROIDS WITH ANESTHETIC PROPERTIES, MEDICAL BIOLOGY 54: 227 (1976).

ISHIKAWA, S, ENDOCRINOLOGY 88: 372 (1971).

KARAVOLAS, H.J., UPTAKE OF [3H]PROGESTERONE AND [3H]5ALPHA-DIHYDROPROGESTERONE BY RAT TISSUES INVIVO AND ANALYSIS OF ACCUMULATED RADIOACTIVITY - ACCUMULATION OF 5ALPHA-DIHYDROPROGESTERONE BY PITUITARY AND HYPOTHALAMIC TISSUES, ENDOCRINOLOGY 98: 164 (1976).

KARAVOLAS, H.J., METABOLISM HORMONAL: 149 (1984).

LEEBLUNDBERG, F, INTERACTIONS OF BARBITURATES OF VARIOUS PHARMACOLOGICAL CATEGORIES WITH BENZODIAZEPINE RECEPTORS, MOLECULAR PHARMACOLOGY 21: 320 (1982).

Leeb-Lundberg, F., Proceedings of the National Academy of Sciences of the United States of America 77: 7468 (1980).

LODGE, D, EFFECTS OF KETAMINE AND 3 OTHER ANESTHETICS ON SPINAL REFLEXES AND INHIBITIONS IN THE CAT, BRITISH JOURNAL OF ANAESTHESIA 56: 1143 (1984).

MAJEWSKA, M.D., MOL PHARM 25: 353 (1984).

10.1126/science.6248961

MCEWEN, B.S., ADRENAL ACTIONS BRAI: 1 (1982).

NICOLL, R.A., PROLONGATION OF HIPPOCAMPAL INHIBITORY POSTSYNAPTIC POTENTIALS BY BARBITURATES, NATURE 258: 625 (1975).

OLSEN, R.W., DRUG-INTERACTIONS AT THE GABA RECEPTOR-IONOPHORE COMPLEX, ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY 22: 245 (1982).

PAUL, S.M., THE BENZODIAZEPINE - GABA - CHLORIDE IONOPHORE RECEPTOR COMPLEX - COMMON SITE OF MINOR TRANQUILIZER ACTION, BIOLOGICAL PSYCHIATRY 16: 213 (1981).

Paul, S. M., Science 233:228 (1986).

PUIL, E, INTERNAL CESIUM IONS BLOCK VARIOUS-K CONDUCTANCES IN SPINAL MOTO-NEURONS, CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY 59: 1280 (1981).

RAMANJANEYULU, R, BINDING CHARACTERISTICS AND INTERACTIONS OF DEPRESSANT DRUGS WITH [S-35]TERT-BUTYLBICYCLOPHOSPHOROTHIONATE, A LIGAND THAT BINDS TO THE PICROTOXININ SITE, JOURNAL OF NEUROCHEMISTRY 42: 221 (1984).

RIKKER, J, ADRENAL ACTIONS BRAI: 69 (1982).

ROMMERTS, F.E., OCCURRENCE AND LOCALIZATION OF 5ALPHA-STEROID REDUCTASE, 3ALPHA-HYDROXYSTEROID AND 17BETA-HYDROXYSTEROID DEHYDROGENASES IN HYPOTHALAMUS AND OTHER BRAIN TISSUES OF MALE RAT, BIOCHIMICA ET BIOPHYSICA ACTA 248: 489 (1971).

SCHAMBELAN, M, DEOXYCORTICOSTERONE PRODUCTION AND REGULATION IN MAN, JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM 34: 695 (1972).

SCHOLFIELD, C.N., POTENTIATION OF INHIBITION BY GENERAL-ANESTHETICS IN NEURONS OF THE OLFACTORY CORTEX INVITRO, PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY 383: 249 (1980).

Schwartz R. D. GABAergic transmission and anxiety (1986).

SCHWARTZ, R.D., BARBITURATE AND PICROTOXIN-SENSITIVE CHLORIDE EFFLUX IN RAT CEREBRAL CORTICAL SYNAPTONEUROSOMES, FEBS LETTERS 175: 193 (1984).

SCHWARTZ, R.D., CHARACTERIZATION OF BARBITURATE-STIMULATED CHLORIDE EFFLUX FROM RAT-BRAIN SYNAPTONEUROSOMES, JOURNAL OF NEUROSCIENCE 5: 2963 (1985).

SEGAL, M, RAT HIPPOCAMPAL-NEURONS IN CULTURE - RESPONSES TO ELECTRICAL AND CHEMICAL STIMULI, JOURNAL OF NEUROPHYSIOLOGY 50: 1249 (1983).

SEGAL, M, RAT HIPPOCAMPAL-NEURONS IN CULTURE - VOLTAGE-CLAMP ANALYSIS OF INHIBITORY SYNAPTIC CONNECTIONS, JOURNAL OF NEUROPHYSIOLOGY 52: 469 (1984).

SELYE, H, Anesthetic effect of steroid hormones, PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE 46: 116 (1941).

SIGEL, E, A GAMMA-AMINOBUTYRIC ACID BENZODIAZEPINE RECEPTOR COMPLEX FROM BOVINE CEREBRAL-CORTEX - IMPROVED PURIFICATION WITH PRESERVATION OF REGULATORY SITES AND THEIR INTERACTIONS, JOURNAL OF BIOLOGICAL CHEMISTRY 259: 7219 (1984).

SIMMONDS, M.A., EVIDENCE THAT BICUCULLINE AND PICROTOXIN ACT AT SEPARATE SITES TO ANTAGONIZE GAMMA-AMINOBUTYRIC ACID IN RAT CUNEATE NUCLEUS, NEUROPHARMACOLOGY 19: 39 (1980).

SKOLNICK, P, BENZODIAZEPINE RECEPTORS IN THE CENTRAL NERVOUS-SYSTEM, INTERNATIONAL REVIEW OF NEUROBIOLOGY 23: 103 (1982).

10.1126/science.6258230

SQUIRES, R.F., [S-35]TERT-BUTYLBICYCLOPHOSPHOROTHIONATE BINDS WITH HIGH-AFFINITY TO BRAIN-SPECIFIC SITES COUPLED TO GAMMA-AMINOBUTYRIC ACID-A AND ION RECOGNITION SITES, MOLECULAR PHARMACOLOGY 23: 326 (1983).

Study, R. E., Proceedings of the National Academy of Sciences of the United States of America 78: 7180 (1981).

STUMPF, W.E., STEROID HORMONE REGU: 41 (1980).

TALLMAN, J.F., GABAERGIC MODULATION OF BENZODIAZEPINE BINDING-SITE SENSITIVITY, NATURE 274: 383 (1978).

10.1126/science.6101294

THAGARAJAN, R, J NEUROCHEM 41: 578 (1983).

TRIFILETTI, R.R., EUR J PHARMACOL 106: 441 (1985).

WEIBE, J.W., STEROIDS 35: 561 (1980).

Cottrell G. L. Journal of Physiology in press.