Adrenergic Receptors in Human Liver Plasma Membranes: Predominance of β2- and α1-Receptor Subtypes*

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Abstract
Adrenergic receptors in human liver plasma membranes were characterized by radioligand binding assays. The binding of [3H] dihydroalprenolol ([3H]DHA) to partially purified membranes was rapid, of high affinity, saturable, and stereospecific. The binding of [125I]iodocyanopindolol to the same membranes was also saturable and stereospecific, but extremely slow, and at 37 C required about 6 h for equilibration. The maximum number of binding sites from six livers determined with these two β-receptor ligands was 36–83 fmol/mg protein. Catecholaminergic agonists competed for these binding sites in the order typical for β2-adrenergic receptors. IPS 339 [(tertiarybutylamino-3-ol-2-propyl)oximino-9-fluorene hydrochloride], a β2-selective antagonist, was at least 3 orders of magnitude more potent in inhibiting the binding of [3H]DHA than the β1-antagonist, atenolol. Computer-aided analysis of the competition curves as well as Hofstee transformations of the binding data indicated the predominance of the β2subtype. The GTP analog guanyl-5 ′ -yl-imidodiphosphate, decreased the binding affinity of the agonist, l-isoproterenol, indicating the modulation of agonist-promoted coupling of the receptors to guanine nucleotide regulatory proteins. The maximum number of binding sites for the binding of [3H]prazosin and [3H]dihydroergocryptine were the same (60–70 fmol/mg protein), indicating that the majority of the α-receptors are of the α1-subtype. Competition experiments with prazosin and yohimbine confirmed the predominance of the α1-receptor subtype, although the presence of α2-receptors cannot be completely ruled out. These results indicate that adrenergic receptors in human liver plasma membranes are predominantly of the β2- and α1-subtypes