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The monoamines and their cognate receptors are widespread in the central nervous system and are vital for normal brain function. Dysfunction in these systems underlies several psychiatric and neurological disease states, and consequently monoamines are targets of a host of pharmacotherapies. This review provides an overview on how monoamine receptors are regulated by adaptor proteins and lipid rafts with emphasis on interactions in nerve cells. Monoamine receptors have prominent intracellular loops that provide binding sites for adaptor proteins. Receptor function is further modulated by cholesterol and submembranous microdomains termed lipid rafts. These interactions determine several facets of G protein–coupled receptor (GPCR) function including trafficking, localization, and signaling. Possible roles of adaptor proteins and lipid rafts in disease states and in mediating actions of drugs and therapeutic agents are also discussed.
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