Anti-Idiotypic Antibodies That Mimic Opioids
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The existence of opioid receptors as “narcotic analgesic binding components” in mammalian brain was first documented in the early 1970s (1 –3 ). Shortly thereafter, endogenous opioid peptides (endorphins) that also bound to these receptors were found in mammalian brain tissue. Subsequent pharmacological work revealed the existence of three main subclasses of receptors designated �, δ, and κ. This work was confirmed by the recent cloning of these three subclasses (4 –8 ) that bear sequence homologies to each other and to the G-protein-coupled receptor super-family. Before the successes in cloning the subclasses, several investigators seeking to answer questions about the molecular basis of the different opioid-receptor classes prepared anti-idiotypic antibodies to the opioid receptors. This approach was taken because unsuccessful experiments showed that antiopioid-receptor antibodies could not be prepared by immunization with cells expressing the receptors. The general experimental approach has been to use subclass-selective ligands as immunogens to raise antihapten antibodies (Id+ , AB1), which in turn are used as immunogens to prepare anti-idiotypic antibodies (AB2). Anti-idiotypic antibodies have been described in theory as containing an “internal image” of the ligand at their binding site (9 , 10 ). This implies that portions of the binding region of the anti-idiotypic antibody can demonstrate binding properties and, in some cases, pharmacological properties similar to the original ligand. In accordance with this view, the resulting anti-idiotypic anti opioidreceptor antibodies have been shown to mimic their respective agonists both kinetically and pharmacologically (11 –13 ). Thus, antiopioid receptor antibodies have proven to be important tools for studying the functionality and localization of receptors within their native environment (12 ,14 ). A significant advantage to using AB2s as probes for membrane-bound receptors is that they can be fluorescently labeled at sites distant from their receptor-binding site, whereas this cannot be done with the much smaller opioid ligands. Furthermore, fluorescently labeled AB2s can be used to monitor binding to individual cells within a large total population of cells, whereas more commonly used radioreceptor-binding assays can only address the average binding properties of an entire cell population (15 ).