Agmatine: An Endogenous Clonidine-Displacing Substance in the Brain

• Published in: Science (American Association for the Advancement of Science) Vol. 263; no. 5149; pp. 966 - 969
• Main Authors: Li, Gen, Regunathan, S., Barrow, Colin J., Eshraghi, Jamshid, Cooper, Raymond, Reis, Donald J.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 18-02-1994; American Association for the Advancement of Science
• Subjects: Actins; Adrenal Medulla - drug effects; Adrenal Medulla - metabolism; Adrenergic receptors; Agmatine - chemistry; Agmatine - isolation & purification; Agmatine - metabolism; Agmatine - pharmacology; Animals; Arginine; Binding Sites; Biological and medical sciences; Brain - enzymology; Brain - metabolism; Brain Chemistry; Carboxy-Lyases - metabolism; Cattle; Cell membranes; Cells; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Cerebral Cortex - metabolism; Chromaffin cells; Clonidine; Clonidine - analogs & derivatives; Clonidine - metabolism; Enzymes; Epinephrine; Epinephrine - metabolism; Fundamental and applied biological sciences. Psychology; Imidazoline Receptors; Imidazolines; Neurotransmitter Agents - metabolism; Norepinephrine - metabolism; Rats; Receptors; Receptors, Adrenergic, alpha - metabolism; Receptors, Drug - metabolism; Sputum; Ungulates; Vertebrates: nervous system and sense organs; Viscosity; Vertebrata; Mammalia; Rat; Ligand; Rodentia; Central nervous system; Neurotransmitter; Agmatine; Brain (vertebrata); Biological receptor
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.7906055

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.