Agonist-independent regulation of constitutively active G-protein-coupled receptors

G-protein-coupled receptors constitute one of the largest protein superfami lies in mammals. Since the cloning of the encoding genes, these important d rug targets have been subjected to thorough biochemical and pharmacological studies, It has become clear that G-protein-coupled receptors not only tra nsmit signals after stimulation by agonists but can also spontaneously coup le to signal-transduction pathways, Recent findings show that constitutivel y active G-protein-coupled receptors can also be regulated in an agonist-in dependent manner, which has important implications for the interpretation o f the actions of (inverse) agonists and the results of site-directed-mutage nesis studies.