A guanylate cyclase activator (or "GUCA") is a member of a group of proteins that upregulate guanylate cyclase. GUCA is also known as guanylate cyclase-activating protein (or "GCAP"). Its mutations can be associated with vision defects. [1]
There are five genes involved:
There are several therapeutic drugs that act as GUCAs, including linaclotide and plecanatide, which are guanylate cyclase-C receptor agonists. These drugs increase the secretion of bicarbonate and chloride in the colon and potentially relieve visceral hypersensitivity in IBS-C patients. [2]
An acetylcholine receptor is an integral membrane protein that responds to the binding of acetylcholine, a neurotransmitter.
Cyclic guanosine monophosphate (cGMP) is a cyclic nucleotide derived from guanosine triphosphate (GTP). cGMP acts as a second messenger much like cyclic AMP. Its most likely mechanism of action is activation of intracellular protein kinases in response to the binding of membrane-impermeable peptide hormones to the external cell surface. Through protein kinases activation, cGMP can relax smooth muscle. cGMP concentration in urine can be measured for kidney function and diabetes detection.
In biochemistry and pharmacology, receptors are chemical structures, composed of protein, that receive and transduce signals that may be integrated into biological systems. These signals are typically chemical messengers which bind to a receptor and produce physiological responses such as change in the electrical activity of a cell. For example, GABA, an inhibitory neurotransmitter, inhibits electrical activity of neurons by binding to GABAA receptors. There are three main ways the action of the receptor can be classified: relay of signal, amplification, or integration. Relaying sends the signal onward, amplification increases the effect of a single ligand, and integration allows the signal to be incorporated into another biochemical pathway.
Guanylate cyclase is a lyase enzyme that converts guanosine triphosphate (GTP) to cyclic guanosine monophosphate (cGMP) and pyrophosphate:
Guanylate cyclase 2C, also known as guanylyl cyclase C (GC-C), intestinal guanylate cyclase, guanylate cyclase-C receptor, or the heat-stable enterotoxin receptor (hSTAR) is an enzyme that in humans is encoded by the GUCY2C gene.
The alpha-2 (α2) adrenergic receptor is a G protein-coupled receptor (GPCR) associated with the Gi heterotrimeric G-protein. It consists of three highly homologous subtypes, including α2A-, α2B-, and α2C-adrenergic. Some species other than humans express a fourth α2D-adrenergic receptor as well. Catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) signal through the α2-adrenergic receptor in the central and peripheral nervous systems.
The beta-1 adrenergic receptor, also known as ADRB1, can refer to either the protein-encoding gene or one of the four adrenergic receptors. It is a G-protein coupled receptor associated with the Gs heterotrimeric G-protein that is expressed predominantly in cardiac tissue. In addition to cardiac tissue, beta-1 adrenergic receptors are also expressed in the cerebral cortex.
The actions of vasopressin are mediated by stimulation of tissue-specific G protein-coupled receptors (GPCRs) called vasopressin receptors that are classified into the V1 (V1A), V2, and V3 (V1B) receptor subtypes. These three subtypes differ in localization, function and signal transduction mechanisms.
The thromboxane receptor (TP) also known as the prostanoid TP receptor is a protein that in humans is encoded by the TBXA2R gene, The thromboxane receptor is one among the five classes of prostanoid receptors and was the first eicosanoid receptor cloned. The TP receptor derives its name from its preferred endogenous ligand thromboxane A2.
Soluble guanylyl cyclase (sGC) is the only known gasoreceptor for nitric oxide, NO. It is soluble, i.e. completely intracellular. Most notably, this enzyme is involved in vasodilation. In humans, it is encoded by the genes GUCY1A2, GUCY1A3, GUCY1B2 and GUCY1B3.
Retinal guanylyl cyclase 1 also known as guanylate cyclase 2D, retinal is an enzyme that in humans is encoded by the GUCY2D gene.
Natriuretic peptide receptor B/guanylate cyclase B , also known as NPR2, is an atrial natriuretic peptide receptor. In humans it is encoded by the NPR2 gene.
Guanylyl cyclase-activating protein 1 is an enzyme that in humans is encoded by the GUCA1A gene.
Guanylate cyclase soluble subunit beta-1 is an enzyme that in humans is encoded by the GUCY1B3 gene.
Guanylyl cyclase-activating protein 2 is an enzyme that in humans is encoded by the GUCA1B gene. Alternative names:
Guanylate cyclase soluble subunit alpha-3 is an enzyme that in humans is encoded by the GUCY1A3 gene.
Riociguat, sold under the brand name Adempas, is a medication by Bayer that is a stimulator of soluble guanylate cyclase (sGC). It is used to treat two forms of pulmonary hypertension (PH): chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension (PAH). Riociguat constitutes the first drug of the class of sGC stimulators. The drug has a half-life of 12 hours and will decrease dyspnea associated with pulmonary arterial hypertension.
Retinal guanylyl cyclase 2 also known as guanylate cyclase F (GUCY2F) is a protein that in humans is encoded by the GUCY2F gene.
Plecanatide, sold under the brand name Trulance, is a medication for the treatment of chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation. It is being launched in India under the brand name "Plecasoft". Plecanatide is an agonist of guanylate cyclase-C. Plecanatide increases intestinal transit and fluid through a buildup of cGMP.
Scott A. Waldman is an MD and biomedical scientist at Sidney Kimmel Medical College of Thomas Jefferson University, where he is the Samuel M.V. Hamilton Professor of Medicine, and also tenured professor and chair of the Department of Pharmacology & Experimental Therapeutics. He is author of a pharmacology textbook, and former chief editor of Clinical Pharmacology & Therapeutics. He is known for his work in atrial natriuretic factor intracellular signaling through guanylate cyclase (GC), and the relation of Guanylyl cyclase C (GC-C) to the pathogenesis of colorectal cancer. Also for his hypotheses concerning the roles of intestinal paracrine hormones in satiety, obesity and cancer risk. Waldman also holds a concurrent position as adjunct professor at the University of Delaware, School of Health Sciences.