Agmatine: An Endogenous Ligand at Imidazoline Receptors Is a Novel Neurotransmittera
Article first published online: 6 FEB 2006
Annals of the New York Academy of Sciences
How to Cite
REIS, D. J. and REGUNATHAN, S. (1999), Agmatine: An Endogenous Ligand at Imidazoline Receptors Is a Novel Neurotransmitter. Annals of the New York Academy of Sciences, 881: 65–80. doi: 10.1111/j.1749-6632.1999.tb09343.x
- Issue published online: 6 FEB 2006
- Article first published online: 6 FEB 2006
ABSTRACT: Agmatine, an amine and organic cation, is an endogenous ligand at α2-adrenergic and imidazoline (I-) receptors, to which it binds with high affinity. In addition, agmatine has properties of an endogenous neurotransmitter. Thus, agmatine (a) is locally synthesized in brain by a specific enzyme, arginine decarboxylase; (b) is stored in a large number of neurons with selective distribution in the CNS; (c) is associated with small vesicles in axon terminals that, at least in hippocampus, make synaptic asymmetric (excitatory) synapses on pyramidal cells; (d) is released from synaptosomes in a Ca2+-dependent manner; (e) can be enzymatically degraded by agmatinase in synaptosomes; (f) can be inactivated by selective reuptake; (g) blocks the ligand-gated NMDA receptor channel at sites distinct from ligand-binding and polyamine sites; and (h) has systemic actions when administered intraventricularly. Additionally, (i) agmatine is a precursor of brain putrescine and, hence, of higher polyamines, and (j) it competitively inhibits the activity of all isozymes of nitric oxide synthase. Agmatine meets most criteria to establish it as a novel neurotransmitter/neuromodulator in the CNS. However, agmatine differs from forms of clonidine displacing system with respect to distribution, bioactivity, and capacity to interact with antibodies raised to imidazoline-like drugs. Thus, there are multiple endogenous ligands of the imidazoline receptors, one of which is agmatine.