The aims are to develop extensive libraries of polyclonal and monoclonal antibodies to major classes of neurotransmitter receptors including muscarinic cholinergic, alpha and beta-adrenergic, GABAergic and opiates; and to utilize these reagents in studies of receptor structure and function, the degree of molecular homology between receptor subclasses, the localization of neurotransmitter receptors on cell membranes, the evolution of receptor subclasses and the role of anti-receptor antibodies in human diseases. Principal observations include the following: 1) monoclonal antibodies raised against each major class of neurotransmitter receptor recognize the same receptor in a number of different tissues and species suggesting considerable conservation of receptor structure throughout evolution; 2) certain monoclonal antibodies raised against muscarinic cholinergic receptors recognize alpha1-adrenergic receptors and vice versa suggesting structural homology between these pharmacologically distinct receptor sub-types; 3) monoclonal antibodies raised against alpha1-adrenergic receptors recognize alpha2-adrenergic receptors, and this information taken together with pharmacological and biochemical data suggests that alpha1- and alpha2-adrenergic receptors may be closely related """"""""isoreceptors""""""""; 4) monoclonal antibodies to muscarinic cholinergic receptors have been utilized to fluorescently label receptors on the surface of cultured cells and in brain sections demonstrating the potential usefulness of these reagents in studies of receptor localization and distribution in various species and tissues as well as in studies of receptor processing and turnover; and 5) some patients suffering from depression possess autoantibodies to human brain membrane proteins. The identity of these proteins is being pursued.
