Autoantibodies and monoclonal antibodies in the purification and molecular characterization of neurotransmitter receptors

Abstract

The combination of immunological advances with membrane receptor research has promoted rapid progress in the molecular characterization of neurotransmitter receptor molecules. We have to date produced monoclonal antibodies to β₁‐, β₂‐, and β₁‐adrenergic, D₂‐dopaminergic, and muscarinic receptors. In addition we have discovered that some allergic respiratory disease patients possess circulating autoantibodies to β₂‐adrenergic receptors. These antireceptor antibodies in conjunction with specific receptor affinity reagents have allowed us to isolate, purify, and begin to characterize α‐ and β‐adrenergic, dopaminergic, and muscarinic receptors. For example, immunoprecipitation of turkey erythrocyte β₁ receptors with monoclonal antibodies yields a single polypeptide M_r 65–70 K. In contrast, purification of β₂‐adrenergic receptors using either autoantibodies or monoclonal antibodies yields a receptor species with a subunit of M_r 55–59 K. Autoantibodies to β₂ receptors demonstrate a 50–100% homology among β₂ receptors from humans to rats, whereas monoclonal antibody FV‐104 recognizes a determinant in the ligand binding site of all β₁ and β₂ receptors tested to date. These data suggest that β₁‐ and β₂‐adrenergic receptors may have evolved from a common ancestor, perhaps by gene duplication.