Rat Liver β-Adrenergic Receptors: Identification and Characterization with (-)[³H]Dihydroalprenolol

Summary

The potent competitive β-adrenergic antagonist, (-)[³H]dihydroalprenolol, was used to identify binding sites which have the characteristics of β-adrenoreceptors in membranes from rat liver. The binding of (-)[³H]dihydroalprenolol to membranes derived from control and adrenalectomized rats was rapid, reversible and saturable with 60 and 150 fmol bound/mg of protein at saturation, respectively. Half-maximal saturation occurred at 1.5 to 3.5 nM. β-Adrenergic agonists and antagonists competed for the binding sites with a typical β₂-adrenergic specificity. The order of potency of agonists was protokylol > isoproterenol > epinephrine > norepinephrine. (-) Isomers of β-adrenergic agents were consistently more potent than their corresponding (+)isomers to inhibit binding and to activate or inhibit adenylate cyclase. A good correlation was found between the order of potency of various drugs in stimulating or inhibiting the catecholamine-sensitive adenylate cyclase and in competing for the (-)[³H]dihydroalprenolol binding sites (r = 0.95; P < 0.001). Therefore, the (-)[³H]dihydroalprenolol binding sites studied appear to be equivalent to the β-adrenergic receptor in hepatic plasma membranes.

Key-Words:

β-Adrenergic Receptors - Rat Liver - (-)[³ H]-Dihydroalprenolol - Membranes - Agonists - Antagonists