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Phosphodiesterase 1
A phosphodiesterase (PDE) is an enzyme that breaks a phosphodiester bond. Usually, ''phosphodiesterase'' refers to cyclic nucleotide phosphodiesterases, which have great clinical significance and are described below. However, there are many other families of phosphodiesterases, including phospholipases C and D, autotaxin, sphingomyelin phosphodiesterase, DNases, RNases, and restriction endonucleases (which all break the phosphodiester backbone of DNA or RNA), as well as numerous less-well-characterized small-molecule phosphodiesterases. The cyclic nucleotide phosphodiesterases comprise a group of enzymes that degrade the phosphodiester bond in the second messenger molecules cAMP and cGMP. They regulate the localization, duration, and amplitude of cyclic nucleotide signaling within subcellular domains. PDEs are therefore important regulators of signal transduction mediated by these second messenger molecules. History These multiple forms (isoforms or subtypes) of phosph ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
CGMP
CGMP is an initialism. It can refer to: *cyclic guanosine monophosphate (cGMP) *current good manufacturing practice (cGMP) *CGMP, Cisco Group Management Protocol, the Cisco version of Internet Group Management Protocol The Internet Group Management Protocol (IGMP) is a communications protocol used by hosts and adjacent routers on IPv4 networks to establish multicast group memberships. IGMP is an integral part of IP multicast and allows the network to direct mu ... snooping *caseinoglycomacropeptide (CGMP) or caseinomacropeptide; see K-casein *Competitive guaranteed maximum price {{disambiguation ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Cyclic Guanosine Monophosphate
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. Synthesis Guanylate cyclase (GC) catalyzes cGMP synthesis. This enzyme converts GTP to cGMP. Peptide hormones such as the atrial natriuretic factor activate membrane-bound GC, while soluble GC (sGC) is typically activated by nitric oxide to stimulate cGMP synthesis. sGC can be inhibited by ODQ (1H-,2,4xadiazolo ,3-auinoxalin-1-one). Functions cGMP is a common regulator of ion channel conductance, glycogenolysis, and cellular apoptosis. It also relaxes smooth muscle tissues. In blood vessels, relaxation of vascular smooth muscles leads to vasodilation and increased blood flow. At presynaptic terminals in the striatum, cGMP controls the e ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Amino Acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha amino acids appear in the genetic code. Amino acids can be classified according to the locations of the core structural functional groups, as Alpha and beta carbon, alpha- , beta- , gamma- or delta- amino acids; other categories relate to Chemical polarity, polarity, ionization, and side chain group type (aliphatic, Open-chain compound, acyclic, aromatic, containing hydroxyl or sulfur, etc.). In the form of proteins, amino acid '' residues'' form the second-largest component (water being the largest) of human muscles and other tissues. Beyond their role as residues in proteins, amino acids participate in a number of processes such as neurotransmitter transport and biosynthesis. It is thought that they played a key role in enabling life ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Mammals
Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur or hair, and three middle ear bones. These characteristics distinguish them from reptiles (including birds) from which they diverged in the Carboniferous, over 300 million years ago. Around 6,400 extant species of mammals have been described divided into 29 orders. The largest orders, in terms of number of species, are the rodents, bats, and Eulipotyphla (hedgehogs, moles, shrews, and others). The next three are the Primates (including humans, apes, monkeys, and others), the Artiodactyla ( cetaceans and even-toed ungulates), and the Carnivora (cats, dogs, seals, and others). In terms of cladistics, which reflects evolutionary history, mammals are the only living members of the Synapsida (synapsids); this clade, together with Saur ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
PDE1
Phosphodiesterase 1, PDE1, EC 3.1.4.1, systematic name oligonucleotide 5′-nucleotidohydrolase) is a phosphodiesterase enzyme also known as calcium- and calmodulin-dependent phosphodiesterase. It is one of the 11 families of phosphodiesterase (PDE1-PDE11). Phosphodiesterase 1 has three subtypes, PDE1A, PDE1B and PDE1C which divide further into various isoforms. The various isoforms exhibit different affinities for cAMP and cGMP. Discovery The existence of the Ca2+-stimulated Phosphodiesterase 1 was first demonstrated by Cheung (1970), Kakiuchi and Yamazaki (1970) as a result of their research on bovine brain and rat brain respectively. It has since been found to be widely distributed in various mammalian tissues as well as in other eukaryotes. It is now one of the most intensively studied member of the PDE superfamily of enzymes, which today represents 11 gene families, and the best characterized one as well. Further research in the field along with increased availability of ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Splice Variant
Alternative splicing, or alternative RNA splicing, or differential splicing, is an alternative splicing process during gene expression that allows a single gene to code for multiple proteins. In this process, particular exons of a gene may be included within or excluded from the final, processed messenger RNA (mRNA) produced from that gene. This means the exons are joined in different combinations, leading to different (alternative) mRNA strands. Consequently, the proteins translated from alternatively spliced mRNAs will contain differences in their amino acid sequence and, often, in their biological functions (see Figure). Biologically relevant alternative splicing occurs as a normal phenomenon in eukaryotes, where it increases the number of proteins that can be encoded by the genome. In humans, it is widely believed that ~95% of multi-exonic genes are alternatively spliced to produce functional alternative products from the same gene but many scientists believe that most of th ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
PDE4 Inhibitor
A phosphodiesterase-4 inhibitor, commonly referred to as a PDE4 inhibitor, is a drug used to block the degradative action of phosphodiesterase 4 (PDE4) on cyclic adenosine monophosphate (cAMP). It is a member of the larger family of PDE inhibitors. The PDE4 family of enzymes are the most prevalent PDE in immune cells. They are predominantly responsible for hydrolyzing cAMP within both immune cells and cells in the central nervous system. Therapeutic utility The prototypical PDE4 inhibitor is rolipram. PDE4 inhibitors are known to possess procognitive (including long term memory-improving), wakefulness-promoting, neuroprotective, and anti-inflammatory effects. Consequently, PDE4 inhibitors have been investigated as treatments for a diverse group of different diseases, including central nervous system disorders such as major depressive disorder (clinical depression), anxiety disorders, schizophrenia, Parkinson's disease, Alzheimer's disease, multiple sclerosis, attention deficit-hy ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Rolipram
Rolipram is a selective phosphodiesterase-4 inhibitor discovered and developed by Schering AG as a potential antidepressant drug in the early 1990s. It served as a prototype molecule for several companies' drug discovery and development efforts.McKenna, JM and Muller, GW. Medicinal Chemistry of PDE4 Inhibitors. Chapter 33 in Cyclic Nucleotide Phosphodiesterases in Health and Disease, Eds Joseph A. Beavo et al. CRC Press, Dec 5, 2006 Rolipram was discontinued after clinical trials showed that its therapeutic window was too narrow; it could not be dosed at high enough levels to be effective without causing significant gastrointestinal side effects. Rolipram has several activities that make it a continuing focus for research. The etiology of many neurodegenerative diseases involves misfolded and clumped proteins which accumulate in the brain. Cells have a mechanism to dispose of such proteins called the proteasome. However, in Alzheimer's disease and some other conditions t ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
PDE5 Inhibitor
A phosphodiesterase type 5 inhibitor (PDE5 inhibitor) is a vasodilating drug that works by blocking the degradative action of cGMP-specific phosphodiesterase type 5 (PDE5) on cyclic GMP in the smooth muscle cells lining the blood vessels supplying various tissues. These drugs dilate the corpora cavernosa of the penis, facilitating erection with sexual stimulation, and are used in the treatment of erectile dysfunction (ED). Sildenafil was the first effective oral treatment available for ED. Because PDE5 is also present in the smooth muscle of the walls of the arterioles within the lungs, two PDE5 inhibitors, sildenafil and tadalafil, are FDA-approved for the treatment of pulmonary hypertension. As of 2019, the wider cardiovascular benefits of PDE5 inhibitors are being appreciated. Medical uses Phosphodiesterase-5 (PDE5) inhibitors such as sildenafil (Viagra), tadalafil (Cialis), and vardenafil (Levitra) are clinically indicated for the treatment of erectile dysfunction. Sildena ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Sildenafil
Sildenafil, sold under the brand name Viagra, among others, is a medication used to treat erectile dysfunction and pulmonary arterial hypertension. It is unclear if it is effective for treating sexual dysfunction in women. It is taken by mouth or by injection into a vein. Onset is typically within twenty minutes and lasts for about two hours. Common side effects include headaches, heartburn, and flushed skin. Caution is advised in those with cardiovascular disease. Rare but serious side effects include a prolonged erection (priapism) that can lead to damage to the penis, vision problems, and hearing loss. Sildenafil should not be taken by people on nitrates such as nitroglycerin (glycerin trinitrate), as this may result in a serious drop in blood pressure. Sildenafil should not be taken within four hours of taking an alpha blocker. Sildenafil acts by blocking phosphodiesterase 5 (PDE5), an enzyme that promotes breakdown of cGMP, which regulates blood flow in the pe ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Benjamin Weiss (scientist)
Benjamin Weiss (January 26, 1937) is an American neuropharmacologist, Emeritus Professor of Pharmacology and Physiology at Drexel University College of Medicine. He is best known for his work with cyclic nucleotide phosphodiesterases. He was the first to propose, based on his experimental work, that selective inhibition of phosphodiesterases which are expressed differentially in all tissues, could be used as a target for drug development. His work is the basis for many marketed and developmental human drugs that selectively inhibit cyclic nucleotide phosphodiesterases. His investigations on the modulation of adrenergic responses in the pineal gland have resulted in the formation of new concepts that may explain the phenomena of drug tolerance and drug hypersensitivity. He and his laboratory were also instrumental in the development of antisense oligonucleotides and antisense RNA as pharmacological tools to study calmodulin and dopamine receptors, and as pharmacological agents ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
