Agmatine: an Endogenous Clonidine-Displacing Substance in the Brain

American Association for the Advancement of Science (AAAS) - Tập 263 Số 5149 - Trang 966-969 - 1994
Gen Li1, S. Regunathan1, Colin J. Barrow2, Jamshid Eshraghi2, Raymond Cooper2, Donald J. Reis1
1Division of Neurobiology, Department of Neurology and Neuroscience, Cornell University Medical College, New York, NY 10021, USA
2Sterling Winthrop Pharmaceuticals Research Division, Malvern, PA 19355, USA.

Tóm tắt

Clonidine, an antihypertensive drug, binds to α 2 -adrenergic and imidazoline receptors. The endogenous ligand for imidazoline receptors may be a clonidine-displacing substance, a small molecule isolated from bovine brain. This clonidine-displacing substance was purified and determined by mass spectroscopy to be agmatine (decarboxylated arginine), heretofore not detected in brain. Agmatine binds to α 2 -adrenergic and imidazoline receptors and stimulates release of catecholamines from adrenal chromaffin cells. Its biosynthetic enzyme, arginine decarboxylase, is present in brain. Agmatine, locally synthesized, is an endogenous agonist at imidazoline receptors, a noncatecholamine ligand at α 2 -adrenergic receptors and may act as a neurotransmitter.

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Tài liệu tham khảo

ATLAS, D, CLONIDINE-DISPLACING SUBSTANCE (CDS) AND ITS PUTATIVE IMIDAZOLINE RECEPTOR - NEW LEADS FOR FURTHER DIVERGENCE OF ALPHA-2-ADRENERGIC RECEPTOR ACTIVITY, BIOCHEMICAL PHARMACOLOGY 41: 1541 (1991).

ATLAS, D, ISOLATION AND PARTIAL-PURIFICATION OF A CLONIDINE-DISPLACING ENDOGENOUS BRAIN SUBSTANCE, EUROPEAN JOURNAL OF BIOCHEMISTRY 144: 287 (1984).

BUCH, J.K., BIOSYNTHETIC ARGININE DECARBOXYLASE IN ESCHERICHIA-COLI IS SYNTHESIZED AS A PRECURSOR AND LOCATED IN THE CELL-ENVELOPE, JOURNAL OF BACTERIOLOGY 163: 522 (1985).

COUPRY, I, IMIDAZOLINE-GUANIDINIUM RECEPTIVE SITE IN RENAL PROXIMAL TUBULE - ASYMMETRIC DISTRIBUTION, REGULATION BY CATIONS AND INTERACTION WITH AN ENDOGENOUS CLONIDINE DISPLACING SUBSTANCE, JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS 252: 293 (1990).

DIAMANT, S, AN ENDOGENOUS BRAIN SUBSTANCE, CDS (CLONIDINE-DISPLACING-SUBSTANCE), INHIBITS THE TWITCH RESPONSE OF RAT VAS-DEFERENS, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 134: 184 (1986).

DIAMANT, S, A LOW-MOLECULAR WEIGHT BRAIN SUBSTANCE INTERACTS, SIMILARLY TO CLONIDINE, WITH ALPHA-2-ADRENOCEPTORS OF HUMAN-PLATELETS, EUROPEAN JOURNAL OF PHARMACOLOGY 144: 247 (1987).

EINARSSON, S, DETERMINATION OF AMINO-ACIDS WITH 9-FLUORENYLMETHYL CHLOROFORMATE AND REVERSED-PHASE HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY, JOURNAL OF CHROMATOGRAPHY 282: 609 (1983).

ERNSBERGER, P, CHARACTERIZATION AND VISUALIZATION OF CLONIDINE-SENSITIVE IMIDAZOLE SITES IN RAT-KIDNEY WHICH RECOGNIZE CLONIDINE-DISPLACING SUBSTANCE, AMERICAN JOURNAL OF HYPERTENSION 3: 90 (1990).

ERNSBERGER, P, AN ENDOGENOUS SUBSTANCE WITH CLONIDINE-LIKE PROPERTIES - SELECTIVE BINDING TO IMIDAZOLE SITES IN THE VENTROLATERAL MEDULLA, BRAIN RESEARCH 441: 309 (1988).

ERNSBERGER, P, CLONIDINE BINDS TO IMIDAZOLE BINDING-SITES AS WELL AS ALPHA-2-ADRENOCEPTORS IN THE VENTROLATERAL MEDULLA, EUROPEAN JOURNAL OF PHARMACOLOGY 134: 1 (1987).

ERNSBERGER, P, ROLE OF IMIDAZOLE RECEPTORS IN THE VASODEPRESSOR RESPONSE TO CLONIDINE ANALOGS IN THE ROSTRAL VENTROLATERAL MEDULLA, JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS 253: 408 (1990).

ERNSBERGER, P, MOXONIDINE, A CENTRALLY ACTING ANTIHYPERTENSIVE AGENT, IS A SELECTIVE LIGAND FOR I1-IMIDAZOLINE SITES, JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS 264: 172 (1993).

FELSEN, D, CLONIDINE DISPLACING SUBSTANCE IS BIOLOGICALLY-ACTIVE ON SMOOTH-MUSCLE, EUROPEAN JOURNAL OF PHARMACOLOGY 142: 453 (1987).

GOMEZ, R.E., RILMENIDINE LOWERS ARTERIAL-PRESSURE VIA IMIDAZOLE RECEPTORS IN BRAIN-STEM C1 AREA, EUROPEAN JOURNAL OF PHARMACOLOGY 195: 181 (1991).

Himswich W. A. Handbook of Neurochemistry 1 1 : 33 (1969).

Iversen L Handbook of Neurochemistry 1 4 : 197 (1969).

KAMISAKI, Y, BINDING OF [H-3] PARA-AMINOCLONIDINE TO 2 SITES, ALPHA-2-ADRENOCEPTORS AND IMIDAZOLINE BINDING-SITES - DISTRIBUTION OF IMIDAZOLINE BINDING-SITES IN RAT-BRAIN, BRAIN RESEARCH 514: 15 (1990).

KAWABATA, T, OCCURRENCE OF METHYLGUANIDINE AND AGMATINE, NITROSATABLE GUANIDINO COMPOUNDS, IN FOODS, JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 26: 334 (1978).

LORING, R.H., AGMATINE ACTS AS AN ANTAGONIST OF NEURONAL NICOTINIC RECEPTORS, BRITISH JOURNAL OF PHARMACOLOGY 99: 207 (1990).

MAJUMDER, S, BIOCHEMICAL-EVIDENCE FOR THE PRESENCE OF ARGININE DECARBOXYLASE ACTIVITY IN TRYPANOSOMA-CRUZI, JOURNAL OF PARASITOLOGY 78: 371 (1992).

MEELEY, M.P., AN ENDOGENOUS CLONIDINE-DISPLACING SUBSTANCE FROM BOVINE BRAIN - RECEPTOR-BINDING AND HYPOTENSIVE ACTIONS IN THE VENTROLATERAL MEDULLA, LIFE SCIENCES 38: 1119 (1986).

MEELEY, M.P., SOC NEUR ABSTR 15: 1159 (1989).

MICHEL, M.C., ARE THERE MULTIPLE IMIDAZOLINE BINDING-SITES, TRENDS IN PHARMACOLOGICAL SCIENCES 10: 342 (1989).

MICHEL, M.C., KEEPING AN EYE ON THE I-SITE - IMIDAZOLINE-PREFERRING RECEPTORS, TRENDS IN PHARMACOLOGICAL SCIENCES 13: 369 (1992).

MOORE, R.C., NUCLEOTIDE-SEQUENCE AND ANALYSIS OF THE SPEA GENE ENCODING BIOSYNTHETIC ARGININE DECARBOXYLASE IN ESCHERICHIA-COLI, JOURNAL OF BACTERIOLOGY 172: 4631 (1990).

Nichols, A. J., α-Adrenoceptors: Molecular Biology, Biochemistry and Pharmacology: 75 (1991).

PARINI, A, CHARACTERIZATION OF AN IMIDAZOLINE GUANIDINIUM RECEPTIVE SITE DISTINCT FROM THE ALPHA-2-ADRENERGIC RECEPTOR, JOURNAL OF BIOLOGICAL CHEMISTRY 264: 11874 (1989).

QUIK, M, INHIBITION OF NICOTINIC RECEPTOR MEDIATED ION FLUXES IN RAT SYMPATHETIC-GANGLIA BY BGT II-S1 A POTENT PHOSPHOLIPASE, BRAIN RESEARCH 325: 79 (1985).

REGUNATHAN, S, EXPRESSION OF NONADRENERGIC IMIDAZOLINE SITES IN CHROMAFFIN CELLS AND MITOCHONDRIAL-MEMBRANES OF BOVINE ADRENAL-MEDULLA, BIOCHEMICAL PHARMACOLOGY 45: 1667 (1993).

REGUNATHAN, S, EXPRESSION OF NONADRENERGIC IMIDAZOLINE SITES IN RAT CEREBRAL CORTICAL ASTROCYTES, JOURNAL OF NEUROSCIENCE RESEARCH 34: 681 (1993).

REGUNATHAN, S, CLONIDINE-DISPLACING SUBSTANCE FROM BOVINE BRAIN BINDS TO IMIDAZOLINE RECEPTORS AND RELEASES CATECHOLAMINES IN ADRENAL CHROMAFFIN CELLS, MOLECULAR PHARMACOLOGY 40: 884 (1991).

SCHAEFFER, J.M., CHARACTERIZATION OF A HIGH-AFFINITY MEMBRANE-ASSOCIATED ORNITHINE DECARBOXYLASE FROM THE FREE-LIVING NEMATODE CAENORHABDITIS-ELEGANS, BIOCHEMICAL JOURNAL 270: 599 (1990).

SENER, A, STIMULUS-SECRETION COUPLING OF ARGININE-INDUCED INSULIN RELEASE - INSULINOTROPIC ACTION OF AGMATINE, BIOCHEMICAL PHARMACOLOGY 38: 327 (1989).

TABOR, C.W., POLYAMINES, ANNUAL REVIEW OF BIOCHEMISTRY 53: 749 (1984).

TESSON, F, SUBCELLULAR-DISTRIBUTION OF IMIDAZOLINE-GUANIDINIUM-RECEPTIVE SITES IN HUMAN AND RABBIT LIVER - MAJOR LOCALIZATION TO THE MITOCHONDRIAL OUTER-MEMBRANE, JOURNAL OF BIOLOGICAL CHEMISTRY 266: 155 (1991).

TIBIRICA, E, SELECTIVITY OF RILMENIDINE FOR THE NUCLEUS-RETICULARIS LATERALIS, A VENTROLATERAL MEDULLARY STRUCTURE CONTAINING IMIDAZOLINE-PREFERRING RECEPTORS, EUROPEAN JOURNAL OF PHARMACOLOGY 209: 213 (1991).

WANG, H, MOLECULAR PHARMACOLOGY 42: 792 (1992).

WEITZEL, G, HOPPE-SEYLERS ZEITSCHRIFT FUR PHYSIOLOGISCHE CHEMIE 361: 51 (1980).

WIKBERG, JES, EVIDENCE THAT DRUG-BINDING TO NONADRENERGIC [H-3] IDAZOXAN BINDING-SITES (I-RECEPTORS) OCCURS TO INTERACTING OR INTERCONVERTIBLE AFFINITY FORMS OF THE RECEPTOR, PHARMACOLOGY & TOXICOLOGY 70: 208 (1992).

WU, W.H., BIOSYNTHETIC ARGININE DECARBOXYLASE FROM ESCHERICHIA-COLI - PURIFICATION AND PROPERTIES, JOURNAL OF BIOLOGICAL CHEMISTRY 248: 1687 (1973).