Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 18 February 1994:
Vol. 263. no. 5149, pp. 966 - 969
DOI: 10.1126/science.7906055
Prev | Table of Contents | Next

Articles

Science, Vol 263, Issue 5149, 966-969
Copyright © 1994 by American Association for the Advancement of Science

articles

Agmatine: an endogenous clonidine-displacing substance in the brain

G Li, S Regunathan, CJ Barrow, J Eshraghi, R Cooper, and DJ Reis

Department of Neurology and Neuroscience, Cornell University Medical College, New York, NY 10021.

Clonidine, an antihypertensive drug, binds to alpha 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 alpha 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 alpha 2-adrenergic receptors and may act as a neurotransmitter.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Immunoneutralization of Agmatine Sensitizes Mice to {micro}-Opioid Receptor Tolerance.
C. L. Wade, L. L. Eskridge, H. O. X. Nguyen, K. F. Kitto, L. S. Stone, G. Wilcox, and C. A. Fairbanks (2009)
J. Pharmacol. Exp. Ther. 331, 539-546
   Abstract »    Full Text »    PDF »
Receptor-mediated activation of nitric oxide synthesis by arginine in endothelial cells.
M. S. Joshi, T. B. Ferguson Jr., F. K. Johnson, R. A. Johnson, S. Parthasarathy, and J. R. Lancaster Jr. (2007)
PNAS 104, 9982-9987
   Abstract »    Full Text »    PDF »
Arginine Metabolism: Boundaries of Our Knowledge.
S. M. Morris Jr. (2007)
J. Nutr. 137, 1602S-1609S
   Abstract »    Full Text »    PDF »
Activities of DL-{alpha}-Difluoromethylarginine and Polyamine Analogues against Cryptosporidium parvum Infection in a T-Cell Receptor Alpha-Deficient Mouse Model.
N. Yarlett, W. R. Waters, J. A. Harp, M. J. Wannemuehler, M. Morada, J. Bellcastro, S. J. Upton, L. J. Marton, and B. J. Frydman (2007)
Antimicrob. Agents Chemother. 51, 1234-1239
   Abstract »    Full Text »    PDF »
Molecular Basis for the Antiproliferative Effect of Agmatine in Tumor Cells of Colonic, Hepatic, and Neuronal Origin.
C. Wolf, M. Bruss, B. Hanisch, M. Gothert, I. von Kugelgen, and G. J. Molderings (2007)
Mol. Pharmacol. 71, 276-283
   Abstract »    Full Text »    PDF »
Mouse Ornithine Decarboxylase-like Gene Encodes an Antizyme Inhibitor Devoid of Ornithine and Arginine Decarboxylating Activity.
A. J. Lopez-Contreras, C. Lopez-Garcia, C. Jimenez-Cervantes, A. Cremades, and R. Penafiel (2006)
J. Biol. Chem. 281, 30896-30906
   Abstract »    Full Text »    PDF »
The contribution of alpha-1 and alpha-2 adrenoceptors in peripheral imidazoline and adrenoceptor agonist-induced nociception..
A. Dogrul, I. Coskun, and T. Uzbay (2006)
Anesth. Analg. 103, 471-7, table of contents
   Abstract »    Full Text »    PDF »
Protective effect of agmatine on a reperfusion model after transient cerebral ischemia: Temporal evolution on perfusion MR imaging and histopathologic findings..
D.J. Kim, D.I. Kim, S.K. Lee, S.H. Suh, Y.J. Lee, J. Kim, T.S. Chung, and J.E. Lee (2006)
AJNR Am. J. Neuroradiol. 27, 780-785
   Abstract »    Full Text »    PDF »
Pharmacodynamic and Pharmacokinetic Studies of Agmatine after Spinal Administration in the Mouse.
J. C. Roberts, B. M. Grocholski, K. F. Kitto, and C. A. Fairbanks (2005)
J. Pharmacol. Exp. Ther. 314, 1226-1233
   Abstract »    Full Text »    PDF »
Role of L-Arginine in the Pathogenesis and Treatment of Renal Disease.
G. Cherla and E. A. Jaimes (2004)
J. Nutr. 134, 2801S-2806S
   Abstract »    Full Text »    PDF »
The Antinociceptive Potencies and Interactions of Endogenous Ligands During Continuous Intrathecal Administration: Adenosine, Agmatine, and Endomorphin-1.
G. Kekesi, I. Dobos, G. Benedek, and G. Horvath (2004)
Anesth. Analg. 98, 420-426
   Abstract »    Full Text »    PDF »
Dimethylarginine Dimethylaminohydrolase Regulates Nitric Oxide Synthesis: Genetic and Physiological Evidence.
H. Dayoub, V. Achan, S. Adimoolam, J. Jacobi, M. C. Stuehlinger, B.-y. Wang, P. S. Tsao, M. Kimoto, P. Vallance, A. J. Patterson, et al. (2003)
Circulation 108, 3042-3047
   Abstract »    Full Text »    PDF »
Modification of Noradrenaline Release in Pithed Spontaneously Hypertensive Rats by I1-Binding Sites in Addition to alpha 2-Adrenoceptors.
W. Raasch, B. Jungbluth, U. Schafer, W. Hauser, and P. Dominiak (2003)
J. Pharmacol. Exp. Ther. 304, 1063-1071
   Abstract »    Full Text »    PDF »
Agmatine Is Efficiently Transported by Non-Neuronal Monoamine Transporters Extraneuronal Monoamine Transporter (EMT) and Organic Cation Transporter 2 (OCT2).
D. Grundemann, C. Hahne, R. Berkels, and E. Schomig (2003)
J. Pharmacol. Exp. Ther. 304, 810-817
   Abstract »    Full Text »    PDF »
Effects of Polyamines on the Release of Gonadotropin-Releasing Hormone and Gonadotropins in Developing Female Rats.
S. M. Thyssen, P. F. Hockl, A. Chamson, V. A.R. Lux-Lantos, and C. Libertun (2002)
Experimental Biology and Medicine 227, 276-281
   Abstract »    Full Text »    PDF »
Cloning of human agmatinase. An alternate path for polyamine synthesis induced in liver by hepatitis B virus.
S. K. Mistry, T. J. Burwell, R. M. Chambers, L. Rudolph-Owen, F. Spaltmann, W. J. Cook, and S. M. Morris Jr (2002)
Am J Physiol Gastrointest Liver Physiol 282, G375-G381
   Abstract »    Full Text »    PDF »
Polyamine transport system mediates agmatine transport in mammalian cells.
J. Satriano, M. Isome, R. A. Casero Jr., S. C. Thomson, and R. C. Blantz (2001)
Am J Physiol Cell Physiol 281, C329-C334
   Abstract »    Full Text »    PDF »
Regulation of Ornithine Decarboxylase Activity and Polyamine Transport by Agmatine in Rat Pulmonary Artery Endothelial Cells.
P. Babál, M. Ruchko, C. C. Campbell, S. P. Gilmour, J. L. Mitchell, J. W. Olson, and M. N. Gillespie (2001)
J. Pharmacol. Exp. Ther. 296, 372-377
   Abstract »    Full Text »
The Effect of Agmatine Administration on Ischemic-Reperfused Isolated Rat Heart.
S. Greenberg, J. George, Y. Wollman, I. Shapira, S. Laniado, and G. Keren (2001)
Journal of Cardiovascular Pharmacology and Therapeutics 6, 37-45
   Abstract »    PDF »
Nitric Oxide and Central Antihypertensive Drugs : One More Difference Between Catecholamines and Imidazolines.
G. Y. Sy, V. Bruban, P. Bousquet, and J. Feldman (2001)
Hypertension 37, 246-249
   Abstract »    Full Text »    PDF »
Agmatine Inhibits Cell Proliferation and Improves Renal Function in Anti--Thy-1 Glomerulonephritis.
S. ISHIZUKA, R. CUNARD, S. POUCELL-HATTON, L. WEAD, M. LORTIE, S. C. THOMSON, F. B. GABBAI, J. SATRIANO, and R. C. BLANTZ (2000)
J. Am. Soc. Nephrol. 11, 2256-2264
   Abstract »    Full Text »
Agmatine reverses pain induced by inflammation, neuropathy, and spinal cord injury.
C. A. Fairbanks, K. L. Schreiber, K. L. Brewer, C.-G. Yu, L. S. Stone, K. F. Kitto, H. O. Nguyen, B. M. Grocholski, D. W. Shoeman, L. J. Kehl, et al. (2000)
PNAS 97, 10584-10589
   Abstract »    Full Text »    PDF »
Catabolism of arginine and ornithine in the perfused rat liver: effect of dietary protein and of glucagon.
D. O'Sullivan, J. T. Brosnan, and M. E. Brosnan (2000)
Am J Physiol Endocrinol Metab 278, E516-E521
   Abstract »    Full Text »    PDF »
Agmatine Selectively Blocks the N-Methyl-D-Aspartate Subclass of Glutamate Receptor Channels in Rat Hippocampal Neurons.
X.-C. Yang and D. J. Reis (1999)
J. Pharmacol. Exp. Ther. 288, 544-549
   Abstract »    Full Text »
The Effect of Agmatine on Ischemic and Nonischemic Isolated Rat Heart.
S. Greenberg, A. Finkelstein, J. Gurevich, E. Brazowski, F. Rosenfeld, I. Shapira, J. George, S. Laniado, and G. Keren (1999)
Journal of Cardiovascular Pharmacology and Therapeutics 4, 151-158
   Abstract »    PDF »
Agmatine Suppresses Proliferation by Frameshift Induction of Antizyme and Attenuation of Cellular Polyamine Levels.
J. Satriano, S. Matsufuji, Y. Murakami, M. J. Lortie, D. Schwartz, C. J. Kelly, S.-i. Hayashi, and R. C. Blantz (1998)
J. Biol. Chem. 273, 15313-15316
   Abstract »    Full Text »    PDF »
Characterization of I2 Imidazoline and sigma  Binding Sites in the Rat and Human Stomach.
G. J. Molderings, K. Donecker, M. Burian, W. A. Simon, D. W. Schröder, and M. Göthert (1998)
J. Pharmacol. Exp. Ther. 285, 170-177
   Abstract »    Full Text »
Tyramine and Vanadate Synergistically Stimulate Glucose Transport in Rat Adipocytes by Amine Oxidase-Dependent Generation of Hydrogen Peroxide.
L. Marti, N. Morin, G. Enrique-Tarancon, D. Prevot, M. Lafontan, X. Testar, A. Zorzano, and C. Carpéné (1998)
J. Pharmacol. Exp. Ther. 285, 342-349
   Abstract »    Full Text »
Intracellular Signaling Pathways Confer Specificity of Transactivation by Mineralocorticoid and Glucocorticoid Receptors.
S. S. Lim-Tio and P. J. Fuller (1998)
Endocrinology 139, 1653-1661
   Abstract »    Full Text »    PDF »
Involvement of Alpha-2 Adrenoceptors in the Effects of Moxonidine on Intestinal Motility and Fluid Transport.
L. Liu and I. M. Coupar (1997)
J. Pharmacol. Exp. Ther. 283, 1367-1374
   Abstract »    Full Text »
The imidazoline receptor in control of blood pressure by clonidine and allied drugs.
D. J. Reis and J. E. Piletz (1997)
Am J Physiol Regulatory Integrative Comp Physiol 273, R1569-R1571
   Abstract »    Full Text »    PDF »
Is the hypotensive effect of clonidine and related drugs due to imidazoline binding sites?.
P. G. Guyenet (1997)
Am J Physiol Regulatory Integrative Comp Physiol 273, R1580-R1584
   Abstract »    Full Text »    PDF »
Acute Tolerance To Spinally Administered Morphine Compares Mechanistically with Chronically Induced Morphine Tolerance.
C. A. Fairbanks and G. L. Wilcox (1997)
J. Pharmacol. Exp. Ther. 282, 1408-1417
   Abstract »    Full Text »
Stimulation of Imidazoline Receptors Inhibits Proliferation of Human Coronary Artery Vascular Smooth Muscle Cells.
S. Regunathan and D. J. Reis (1997)
Hypertension 30, 295-300
   Abstract »    Full Text »
Clonidine and ST-91 May Activate Imidazoline Binding Sites in the Heart to Release Atrial Natriuretic Peptide.
S. Mukaddam-Daher, C. Lambert, and J. Gutkowska (1997)
Hypertension 30, 83-87
   Abstract »    Full Text »
Immunodetection and Quantitation of Imidazoline Receptor Proteins in Platelets of Patients With Major Depression and in Brains of Suicide Victims.
J. A. Garcia-Sevilla, P. V. Escriba, M. Sastre, C. Walzer, X. Busquets, G. Jaquet, D. J. Reis, and J. Guimon (1996)
Arch Gen Psychiatry 53, 803-810
   Abstract »    PDF »
Aminoguanidine Ameliorates and L-Arginine Worsens Brain Damage From Intraluminal Middle Cerebral Artery Occlusion.
F. Zhang, R. M. Casey, M. E. Ross, and C. Iadecola (1996)
Stroke 27, 317-323
   Abstract »    Full Text »
Discriminative stimulus produced by the imidazoline I2 site ligand, 2 -BFI.
S. Jordan, H.C. Jackson, D.J. Nutt, and S.L. Handley (1996)
J Psychopharmacol 10, 273-278
   Abstract »    PDF »
Imidazoline/Guanidinium Binding Domains on Monoamine Oxidases.
R. Raddatz, A. Parini, and S. M. Lanier (1995)
J. Biol. Chem. 270, 27961-27968
   Abstract »    Full Text »    PDF »
Localization of I[IMAGE]-Imidazoline Binding Sites on Monoamine Oxidases.
F.édér. Tesson, I. Limon-Boulez, P. Urban, M. Puype, J. Vandekerckhove, I. Coupry, D. Pompon, and A. Parini (1995)
J. Biol. Chem. 270, 9856-9861
   Abstract »    Full Text »    PDF »
Identifying clonidine-displacing substance.
D Atlas (1994)
Science 266, 462-464
   PDF »
Response.
D. J. Reis, G. Li, S. Regunathan, C. J. Barrow, and R. Cooper (1994)
Science 266, 463-464
   PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)