ABSTRACT
GPCRs are the largest membrane protein receptor superfamily in the human body, with more than 800 isoforms, and approximately 35% of Food and Drug Administration-approved and marketed drugs currently target GPCRs for the treatment of a wide range of diseases, for heart failure (beta-adrenergic receptors), peptic ulcer (histamine receptors), prostate cancer (gonadotropin receptors), hypertension (adrenergic and angiotensin receptors), pain (opioid receptors), and bronchial asthma (beta2-adrenergic receptors) examples. Although the number of GPCRs is enormous, the signaling proteins downstream of them are limited, heterotrimeric G proteins (GPs) are key proteins that signal GPCRs, translate extracellular stimuli into intracellular responses by coupling to GPCRs and initiate multiple signaling events via downstream cascades. Podocytes are an important component of the glomerular filtration barrier, and their damage is a central event in proteinuria formation and progressive glomerulosclerosis. This article reviews the regulation of GPs, their signaling and their role in podocyte injury to provide a theoretical basis for scientific research and clinical treatment of this disease.
ABSTRACT
In the G protein-coupled receptors (GPCRs) relatively short regions of their intracellular loops and cytoplasmic C-terminal domain are responsible for specific interaction with G-proteins. GPCR-derived peptides corresponding to these regions are able to influence the activity of signal pathways involving the cognate receptors. Modified by hydrophobic radicals, these peptides turn into their cell-penetrating analogs, pepducins, possessing the activity both in vitro and in vivo. This review is devoted to the analysis of the available data and the prospects for GPCR-peptides and their lipophilic derivatives to be used in experimental and clinical medicine in the treatment of vascular diseases, cancers, inflammation, and endocrine dysfunctions.