G-protein-coupled receptors:: an update

The receptors that couple to G proteins (GPCR) and which span the cell membranes seven times (7-TM receptors) were the focus of a symposium in Stockholm 2006. The ensemble of GPCR has now been mapped in several animal species. They remain a major focus of interest in drug development, and their diverse physiological and pathophysiological roles are being clarified, i.a. by genetic targeting. Recent developments hint at novel levels of complexity. First, many, if not all, GPCRs are part of multimeric ensembles, and physiology and pharmacology of a given GPCR may be at least partly guided by the partners it was formed together with. Secondly, at least some GPCRs may be constitutively active. Therefore, drugs that are inverse agonists may prove useful. Furthermore, the level of activity may vary in such a profound way between cells and tissues that this could offer new ways of achieving specificity of drug action. Finally, it is becoming increasingly clear that some of these receptors can signal via novel types of pathways, and hence that 'GPCRs' may not always be G-protein-coupled. Thus there are many challenges for the basic scientist and the drug industry.