Adrenergic receptor subtypes in rabbit iris-ciliary body membranes: Classification by radioligand studies

Receptor subclasses in iris-ciliary body cell membranes were determined by direct binding of radioactive dihydroalprenolol (DHA), yohimbine (YOH), WB-4101 (WB) and prazosin (PRZ), classified respectively as β₁ + β₂, α₂, α₁, and α₁ subtype selective ligands (based on binding to brain adrenergic receptors). Specific binding was defined with appropriate unlabelled agonist and antagonist drugs in each case. Binding data were analysed by library programs of the PROPHET computer system. Subclass specificity was also determined indirectly by binding competition of the labelled ligand (at a three- to 10-fold K_d concentration) with increasing concentrations of 'cold' agonist or antagonist. Ligand binding parameters of unlabelled drugs were obtained from Dixon and Scatchard plots of the data. The adrenergic receptor density of iris-ciliary body is approx. 600 fmol mg^-1 protein, of which 20-25% are primarily β₂ receptors. Three distinct subpopulations of α-receptors, representing 10, 25 and 40-45% of the total, bind PRZ, WB and YOH, respectively, each with high specificity for its corresponding ligand but with 10- to 1000-fold lower specificity for the other two ligands. The majority of α-adrenergic receptors are of the α₂-subtype. A small population of receptors are similar to vascular postsynaptic α₁-receptors, while a larger subpopulation may have characteristics intermediate between α₁- and α₂-subtypes.