Neuroprotective effects of receptor imidazoline 2 and its endogenous ligand agmatine

Receptor imidazoline 2 （I2） is one of the imidazoline receptors with high affinity for [^3H]-idazoxan. Receptor I2, being classified into I2A and I28 subtypes, is mainly localized to the outer membrane of mitochondria in liver, kidney and brain. Receptor I2, displaying high similarity of sequence with monoamine oxidase-B （MAO-B）, is structurally related to MAO-B, but the I2 imidazoline binding site （IEBS） with ligand is distinct from the catalytic site of MAO-B. Agmatine is the endogenous ligand of receptor I2. Accumulating evidence have revealed that the activation of receptors I2 may produce neuroprotective effects by increasing expression of glial fibriUary acidic protein （GFAP） in astrocytes, inhibiting activity of MAO, reducing calcium overload in cells. Agmatine exerts neuroprotection against ischemia-hypoxia, injury, glutamateinduced neurotoxicity by activating imidazoline receptors, blocking N-methyl-D-aspartate （NMDA） receptor, inhibiting all isoforms of nitric oxide synthase （NOS）, and selectively blocking the voltage-gated calcium channels （VGCC）. It would be expected that agmatine is one of the potential neuroprotective agents.

Receptor imidazoline 2 (I2) is one of the imidazoline receptors with high affinity for 3H-idazoxan. Receptor I2,being classified into I2A and I2B subtypes,is mainly localized to the outer membrane of mitochondria in liver,kidney and brain. Receptor I2,displaying high similarity of sequence with monoamine oxidase-B (MAO-B),is structurally related to MAO-B,but the I2 imidazoline binding site (I2BS) with ligand is distinct from the catalytic site of MAO-B. Agmatine is the endogenous ligand of receptor I2. Accumulating evidence have revealed that the activation of receptors I2 may produce neuroprotective effects by increasing expression of glial fibrillary acidic protein (GFAP) in astrocytes,inhibiting activity of MAO,reducing calcium overload in cells. Agmatine exerts neuroprotection against ischemia-hypoxia,injury,glutamate-induced neurotoxicity by activating imidazoline receptors,blocking N-methyl-D-aspartate (NMDA) receptor,inhibiting all isoforms of nitric oxide synthase (NOS),and selectively blocking the voltage-gated calcium channels (VGCC). It would be expected that agmatine is one of the potential neuroprotective agents.