Subtype specificity of alpha-adrenergic receptors in rat heart

Recent studies suggest that two subtypes of alpha-adrenergic receptors (alpha 1 and alpha 2) can be distinguished on the basis of the differential affinities of certain adrenergic ligands for each subtype. We have investigated the binding characteristics of several such ligands for alpha-adrenergic receptors in membrane preparations derived from rat heart. alpha-Adrenergic antagonists competed for binding sites identified by the nonsubtype selective alpha-adrenergic ligand [3H]dihydroergocryptine (DHE) in the order of potency expected for alpha 1-receptors, namely, prazosin (EC50 = 0.35 nM) greater than phentolamine (EC50 = 37 nM) greater than yohimbine (EC50 = 918 nM). Furthermore, the nonsubtype selective radioligand [3H]DHE identified a quantitatively similar number of specific binding sites in rat cardiac membranes as the alpha 1-selective radioligand [3H]prazosin (33 and 36 fmoles/mg protein, respectively), while the alpha 2-selective ligand [3H]clonidine at concentrations up to 20 nM demonstrated negligible specific binding. We conclude that the alpha-adrenergic receptors of rat heart homogenates demonstrate binding characteristics typical of alpha 1-receptors. While we cannot exclude the presence of small numbers of alpha-2 receptors, the similar number of binding sites identified at saturation for the alpha 1-specific ligand [3H]prazosin and for the nonsubtype selective ligand [3H]DHE supports the hypothesis that the alpha-receptors of rat heart are predominantly of the alpha 1-subtype.