OCULAR ALPHA(2)-RECEPTOR SUBCLASSES AND ANTIGLAUCOMA EFFICACY

An overview of the ocular hypotensive actions of some alpha(2)-agonist s with imidazoline structures is presented. These agents inhibit isopr oterenol-stimulated adenylate cyclase (AC) activity in ciliary process membrane through a Na+ and GTP-dependent mechanism. Receptor binding studies with the alpha(2)-agonist radioligand I-125 p-iodoclonidine (I-125PIC) in rabbit ciliary body membranes indicate that the alpha( 2)-receptor subtype is alpha(2A). Gpp(NH)p and NaCl dose-dependently d ecreased the number of I-125PIC binding sites by shifting the recept or-G protein complexs from the high affinity state to the low affinity state for agonist binding. This is consistent with the observations t hat inhibition of AC was Na+ and GTP dependent. The NaCl and Gpp(NH)p effects on binding appeared to be through different mechanisms. The al pha(2)-receptor in ciliary process thus appears to be an alpha(2A)-rec eptor that is negatively coupled to the AC-cAMP generating system.