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Agmatine: An Endogenous Ligand at Imidazoline Receptors Is a Novel Neurotransmitter a
Author(s) -
REIS DONALD J.,
REGUNATHAN SOUNDARARAJAN
Publication year - 1999
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1999.tb09343.x
Subject(s) - agmatine , imidazoline receptor , chemistry , arginine decarboxylase , ligand (biochemistry) , receptor , nmda receptor , monoamine neurotransmitter , ifenprodil , neurotransmitter , biochemistry , arginine , pharmacology , biology , serotonin , amino acid
Agmatine, an amine and organic cation, is an endogenous ligand at α 2 ‐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 Ca 2+ ‐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.