Different affinities of α2-agonists for imidazoline and α2-adrenergic receptors

Abstract

It has recently been shown that imidazoline α2-adrenergic agonists, such as clonidine and UK 14,304 selectively bind to both α2- and imidazoline receptors in basolateral membranes from rabbit renal proximal tubule. In order to define the relative affinity of three antihypertensive α2-agonists for the two classes of receptors, we performed competition studies of imidazoline α2-antagonist 3H-RX 781094 and nonimidazoline antagonist 3H-rauwolscine binding to basolateral membranes from rabbit proximal tubule. The order of potency for inhibition of radioligand binding to basolateral membranes was rilmenidine > clonidine > guanfacine and clonidine > guanfacine > rilmenidine for 3H-RX 781094 and 3H-rauwolscine binding, respectively. These data show that not only clonidine, but also rilmenidine and guanfacine, drugs usually used as specific α2-agonists, bind to both α2- and imidazoline receptors. The higher affinity of these molecules for one of the other class of receptors could explain their different capacity to induce hypotension and side effects.