G protein-coupled receptors: abnormalities in signal transmission, disease states and pharmacotherapy.

The aim of this review is to present the research results and draw new conclusions about the impact of alterations in the signal transmission through the G protein-coupled receptors (GPCRs) on the formation of diseases and drug therapy. GPCR family is the largest and the most diverse group of membrane receptors. They transmit signals into the cell by interaction with different ligands, which include, inter alia, hormones, neurotransmitters, and photons. GPCRs are responsible for the proper conduction of many physiological processes such as vision, intercellular communication, the neuronal transmission, hormonal signaling and are involved in many pathological processes. They are also point on the binding pathway of multiple drugs. They are targets of nearly one third of the drugs at the current pharmaceutical market. The genes encoding GPCRs represent about 4% of the human genome. Mutations that occur in them are associated with a broad spectrum of diseases of diverse etiology. As a mutations result, there is a change in receptor activity (GPCR become inactive, overactive, or constitutively active), in the process of ligand binding and signal transduction. Changes in the GPCRs functioning can cause diseases such as retinitis pigmentosa (rhodopsin mutations), nephrogenic diabetes insipidus (vasopressin receptor mutations), obesity (melanocortin receptor mutations). Many mutational changes in genes encoding GPCR can change drug therapy of already existed diseases: heart failure (adrenergic receptors), asthma (cysteinyl leukotriene receptors). Studies concerning the structure and function of genetically modified GPCRs allow to get know a variety of mechanisms of its action, which in turn can contribute to broaden the knowledge on the etiology and pharmacotherapy of many currently incurable diseases.