Possible structural and functional relationships between imidazoline receptors and alpha 2-adrenoceptors.
Although it is now well established that imidazoline receptors and alpha 2-adrenoceptors are discrete entities with distinct endogenous ligands, the two receptor classes apparently have several common features. While the catecholamines stimulate alpha 2-adrenoceptors but not imidazoline receptors, agmatine, a guanidine analog that may be an endogenous imidazoline receptor ligand, can interact with both I1 and I2 imidazoline receptors as well as alpha 2-adrenoceptors, although, interestingly, other guanidines such as guanabenz are highly selective for alpha 2-adrenoceptors versus I1 receptors. Most I1 receptor agonists such as moxonidine, rilmenidine, and clonidine can also stimulate alpha 2-adrenoceptors, and the same physiological response is produced by activation of central I1 receptors and alpha 2-adrenoceptors, but their anatomical locations differ. The imidazoline idazoxan is an antagonist at I1, I2, and alpha 2-receptors, but minor structural alterations of idazoxan can result in molecules with selectivity for either alpha 2-adrenoceptors or imidazoline receptors. The precise mode of interaction of imidazoline agonists and antagonists with the alpha 2-adrenoceptor is not yet understood, and structures of the imidazoline receptors are still unknown. Nevertheless, the fact that many agents can stimulate or block both receptor classes, combined with the fact that alpha 2-adrenoceptors and I1 receptors can mediate identical physiological responses, suggests that many common structural features may be present.
Hieble
J P
JP
Division of Pharmacological Sciences, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406, USA.
Ruffolo
R R
RR
D000818:Animals; D001665:Binding Sites; D007093:Imidazoles / Q000378:metabolism*; D054755:Imidazoline Receptors; D008024:Ligands; D018341:Receptors, Adrenergic, alpha-2 / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism*; D011955:Receptors, Drug / Q000737:chemistry* / Q000145:classification / Q000187:drug effects / Q000378:metabolism*; D013329:Structure-Activity Relationship
D007093:Imidazoles; D054755:Imidazoline Receptors; D008024:Ligands; D018341:Receptors, Adrenergic, alpha-2; D011955:Receptors, Drug