Mammalian β₁- and β₂-adrenergic receptors. Immunological and structural comparisons

β₁- and β₂-adrenergic receptors, pharmacologically distinct proteins, have been reported to be structurally dissimilar. In the present study three techniques were employed to compare the nature of mammalian β₁- and β₂-adrenergic receptors. Antibodies against each of the receptor subtypes were raised separately. Polyclonal antisera against β₁-receptors of rat fat cells were raised in mice, and antisera against β₂-receptors of guinea pig lung were raised in rabbits. Receptors purified from rat fat cells (β₁-), S49 mouse lymphoma cells (β₂-), and rat liver (β₂-) were probed with these antisera. Each anti-receptor antisera demonstrated the ability to immunoprecipitate purified receptors of both β₁- and β₂-subtypes. The mobility of β-receptors subjected to polyacrylamide gel electrophoresis was probed using anti-receptor antibodies and nitrocellulose blots of the gels. Fat cell β₁-adrenergic receptors display M(r) = 67,000 under reducing conditions and M(r) = 54,000 under nonreducing conditions, as previously reported. Both β₁- and β₂-receptors displayed this same shift in electrophoretic mobility observed in the presence as compared to the absence of disulfide bridge-reducing agents, as detected both by autoradiography of the radiolabeled receptors and by immunoblotting of native receptors. Finally, isoelectric focusing of purified radioiodinated β₁- and β₂-adrenergic receptors revealed identical isoelectric points. These data are the first to provide analyses of immunological, structural, and biochemical features of β₁- and β₂-subtypes in tandem and underscore the structural similarities that exist between these pharmacologically distinct receptors.