May 27, 2014
Synonyms
Seven transmembrane helix receptors; Heptahelical receptors; Serpentine receptors
Definition
G-protein-coupled receptors (GPCRs) are a large family of plasma membrane receptors. Upon binding its agonist, a GPCR activates an intracellular heterotrimeric guanine nucleotide regulatory protein (G protein). The activated G protein modulates the activity of one or more enzymes or ion channels. G protein independent signaling pathways have also been identified for several receptors.
Basic Characteristics
Cells receive much of the information about their external environment by way of receptor proteins that span the plasma membrane. GPCRs are the largest family of plasma membrane receptors. They mediate response to the majority of hormones and neurotransmitters as well as the senses of sight, smell, and taste. These receptors have in common a seven transmembrane topology and functional interactions with heterotrimeric guanine nucleotide binding proteins (G proteins). GPCRs respond to a large variety of stimuli ranging from photons, ions, amino acids, and small organic molecules to peptide and protein hormones.
Analysis of the human genome reveals over 800 unique GPCRs [1]. The functional role for many of these GPCRs has not yet been determined and these have been designated as orphan GPCRs. GPCRs can be divided into five families based on sequence homology: the rhodopsin family, the secretin receptor family, the glutamate receptor family, the adhesion receptor family, and the frizzled/TAS2 receptor family. The rhodopsin family is by far the largest with over 700 members. Of these 460 belong to the subfamily of odorant receptors, and the rest are receptors for hormones and neurotransmitters.
GPCRs as a group constitute the largest family of targets for pharmacological intervention. They are critically involved in virtually every physiological system. A partial list of natural GPCR ligands includes protons, calcium, glutamate, GABA, acetylcholine, histamine, GTP/ATP, adenosine, cAMP, melatonin, epinephrine, serotonin, and dopamine. Peptide hormone GPCR activators include angiotensin, vasopressin, bradykinin, calcitonin, FSH, glucagon, somatostatin and a host of chemokines, opioids, and cannabinoids. Olfactory and gustatory sensory transduction involves GPCRs responsive to a large array of odorants and pheromones, and vision depends on the light-activated ligand retinal covalently bound to its own GPCR rhodopsin.
The electronic version of this article is the complete one and can be found online at: http://www.springerreference.com/docs/html/chapterdbid/137855.html
