Narcotic binding to membrane acidic lipids

Most putative neurotransmitters, including the bioamines such as norepinephrine, dopamine, 5-hydroxytryptamine, histamine and acetylcholine appear to mediate highly specific biological actions at membrane sites, even though their structures are flexible. In this regard, it is quite possible that certain membrane acidic lipids can interact selectively with a particular cationic drug to elicit its biological action. Some samples of the selective bioamine binding have already been discussed. Among several membrane acidic lipids examined, CS was found to exhibit: the highest increase of selective binding with opiates, a remarkable correlation between affinity and analgetic potency, and the ability to discriminate between agonists and antagonists. Moreover, the molecular configuration of CS can accommodate most of the structure of opiates and provide logical explanations for structure-activity relationships. Furthermore, in vivo evidence supports an important role for CS in morphine action. When the availability of CS is decreased, responsiveness to morphine occurs. A genetic mutant, Jimpy mice, which are known to have a low content of cerebroside sulfate were found to be less sensitive to morphine with respect to analgetic activity and have lower capacity for binding morphine when compared with their littermate controls. Moreover, Azure A, a cationic dye which binds selectively with CS, decreased morphine binding and analgetic activity. These findings provide strong argument that CS may be a binding component of an opiate receptor.