GPCR expression in the heart; "new" receptors in myocytes and fibroblasts.

G protein-coupled receptor (GPCR) signaling cascades play a key role in regulation of the cardiovascular system. GPCRs comprise the largest cell-surface receptor superfamily and are also the largest class of drug targets to which agonists and antagonists are currently directed. This article reviews recent data regarding aspects of GPCR signaling and emphasizes the recent "discovery" of expression of "new" GPCRs in cardiac myocytes and fibroblasts. In addition to several well-known ("classical") GPCRs that are expressed by cardiac myocytes and fibroblasts, these cell types or cardiac tissue (cell types as-yet undefined) express a large number of other GPCRs, including receptors for peptides, lipids, and other molecules, as well as "orphan" receptors for which the natural agonists and (patho)physiologic roles in the cardiovascular system have not yet been defined. Studies of the newly recognized GPCRs-in particular, deorphanization of novel GPCRs and experiments that define their signal pathways, expression patterns, desensitization mechanisms, cross-talk with other receptors, and genetic variation-are likely to yield important new insights into cardiovascular cell function. Moreover, these "new" GPCRs are attractive targets for the development of drugs for the treatment of cardiac and other cardiovascular disorders.