Heterogeneity of alpha₁ receptors associated with vascular smooth muscle: Evidence from functional and ligand binding studies

The nature of the alpha₁ receptor associated with rabbit aorta has been examined in functional and receptor binding studies. In isolated aortic rings the dose-response curve for (-)metaraminol was not parallel to that of (-)epinephrine, (-)norepinephrine or (-)phenylephrine. Following inactivation of a portion of the alpha receptors with phenoxybenzamine, the occupancy versus response relationship for metaraminol, in contrast to the other test agonists, was biphasic. These results suggest the possibility that metaraminol interacts with different functional groups on the alpha₁ receptor than the other test agonists. In microsomes prepared from frozen aorta, metaraminol bound to two classes of sites (K_H = 0.41 ± 0.12 μM, K_L = 39.1 ± 7.1 μM) labelled by the selective alpha₁ antagonist [³H] prazosin. Similar binding characteristics were observed in microsomes prepared from aorta shipped in serum on ice or aorta from animals killed in our laboratory. Norepinephrine also bound to two sites on the alpha receptor in all three preparations tested (K_H = 0.06 ± 0.01 μM, K_L = 5.09 ± 2.4 μM; estimated from frozen aorta). The Scatchard plot of [³H] prazosin binding to microsomes prepared from frozen aorta was curvilinear. Estimates of the affinities and site densities were 49.6 ± 15.3 pM and 44.8 ± 11.8 pmol/gm protein and 1.0 ± 0.2 nM and 43.8 ± 17.4 pmol/gm for the high and low affinity sites, respectively. These data are consistent with the idea that there are subtypes of the alpha₁ receptor.