Imidazoline Receptors
Imidazoline binding sites were originally classified into I1 sites (labeled by clonidine) and I2 sites (labeled by idazoxan). I2 sites have been further classified into I2A (amiloride-sensitive) and I2B (amiloride-insensitive). A putative I3 has been described which enhances insulin secretion. Imidazoline receptors are orphan proteins and their biological function has primarily been established by binding of selective ligands, although their protein identity has yet to be determined.
Imidazoline receptors have a physiological role in the central regulation of blood pressure. Activation of I1 receptors decreases sympathetic tone via a central mechanism, which has a hypotensive effect and reduces plasma catecholamine levels. In contrast, I2-mediated monoamine oxidase inhibition has a hypertensive effect and increases plasma catecholamine levels.
Properties of Imidazoline Receptors
| Receptor | I1 | I2 | I3 |
|---|---|---|---|
| Location | Lateral reticular nucleus, locus ceruleus, kidney, platelets, pancreas | Interpeduncular and arcuate nuclei, pineal gland, liver, kidney, heart, striated muscle, MAO | Pancreatic β cells |
| Transduction Mechanism | ↑ Diacylglycerol and arachidonic acid | Unknown | Unknown |
| Key Selective Ligands |
AGN 192403 (1072) Clonidine (0690) Rilmenidine (0790) |
BU 239 (0726) RS 45041-190 (0889) 2-BFI (0348) |
KU14R (1131) |
| Putative Endogenous Ligands | Agmatine (0842), Harmane (1132) | ||