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Adrenoceptors
The adrenergic receptors or adrenoceptors are a class of G protein-coupled receptors that are targets of many catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) produced by the body, but also many medications like beta blockers, beta-2 (β2) agonists and alpha-2 (α2) agonists, which are used to treat high blood pressure and asthma, for example. Many cells have these receptors, and the binding of a catecholamine to the receptor will generally stimulate the sympathetic nervous system (SNS). The SNS is responsible for the fight-or-flight response, which is triggered by experiences such as exercise or fear-causing situations. This response dilates pupils, increases heart rate, mobilizes energy, and diverts blood flow from non-essential organs to skeletal muscle. These effects together tend to increase physical performance momentarily. History By the turn of the 19th century, it was agreed that the stimulation of sympathetic nerves could cause different ...
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Epinephrine
Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands and by a small number of neurons in the medulla oblongata. It plays an essential role in the fight-or-flight response by increasing blood flow to muscles, heart output by acting on the SA node, pupil dilation response, and blood sugar level. It does this by binding to alpha and beta receptors. It is found in many animals, including humans, and some single-celled organisms. It has also been isolated from the plant ''Scoparia dulcis'' found in Northern Vietnam. Medical uses As a medication, it is used to treat several conditions, including allergic reaction anaphylaxis, cardiac arrest, and superficial bleeding. Inhaled adrenaline may be used to improve the symptoms of croup. It may also be used for asthma when other treatments are not e ...
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Epinephrine
Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands and by a small number of neurons in the medulla oblongata. It plays an essential role in the fight-or-flight response by increasing blood flow to muscles, heart output by acting on the SA node, pupil dilation response, and blood sugar level. It does this by binding to alpha and beta receptors. It is found in many animals, including humans, and some single-celled organisms. It has also been isolated from the plant ''Scoparia dulcis'' found in Northern Vietnam. Medical uses As a medication, it is used to treat several conditions, including allergic reaction anaphylaxis, cardiac arrest, and superficial bleeding. Inhaled adrenaline may be used to improve the symptoms of croup. It may also be used for asthma when other treatments are not e ...
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Raymond Ahlquist
Raymond Perry Ahlquist (July 26, 1914 – April 15, 1983) was an American pharmacist and pharmacologist. He published seminal work in 1948 that divided adrenoceptors into α- and β-adrenoceptor subtypes. This discovery explained the activity of several existing drugs and also laid the ground work for new drugs including the widely prescribed beta blockers. Early life and education Ahlquist was born on July, 26 1914 in Missoula, Montana. Both of his parents came from Sweden. His father was an auditor at the Railway Company Northern Pacific Railway. In 1940, Ahlquist graduated with a Ph.D. degree in pharmacology from the University of Washington in Seattle, the first person to be awarded such a degree from that institution. Career and research Ahlquist spent four years as a faculty member at South Dakota State University in Brookings. In 1944 he became Assistant Professor of Pharmacology at the Medical College of Georgia in Augusta. In 1946 he was appointed Associate Profe ...
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Alpha-2 Adrenergic Receptor
The alpha-2 (α2) adrenergic receptor (or adrenoceptor) 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. Cellular localization The α2A adrenergic receptor is localised in the following central nervous system (CNS) structures: * Brainstem (especially the locus coeruleus) * Midbrain * Hypothalamus * Hippocampus * Spinal cord * Cerebral cortex * Cerebellum * Septum Whereas the α2B adrenergic receptor is localised in the following CNS structures: * Olfactory system * Thalamus * Pyramidal layer of the hippocampus * Cerebellar Purkinje layer and the α2C adrenergic receptor is localised in the CN ...
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Beta-3 Adrenergic Receptor
The beta-3 adrenergic receptor (β3-adrenoceptor), also known as ADRB3, is a beta-adrenergic receptor, and also denotes the human gene encoding it. Function Actions of the β3 receptor include *Enhancement of lipolysis in adipose tissue. *Thermogenesis in skeletal muscle Page 163 It is located mainly in adipose tissue and is involved in the regulation of lipolysis and thermogenesis. Some β3 agonists have demonstrated antistress effects in animal studies, suggesting it also has a role in the central nervous system (CNS). β3 receptors are found in the gallbladder, urinary bladder, and in brown adipose tissue. Their role in gallbladder physiology is unknown, but they are thought to play a role in lipolysis and thermogenesis in brown fat. In the urinary bladder it is thought to cause relaxation of the bladder and prevention of urination. Mechanism of action Beta adrenergic receptors are involved in the epinephrine- and norepinephrine-induced activation of adenylate cyclase th ...
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Beta Blocker
Beta blockers, also spelled β-blockers, are a class of medications that are predominantly used to manage cardiac arrhythmia, abnormal heart rhythms, and to protect the heart from a second myocardial infarction, heart attack after a first heart attack (preventative healthcare, secondary prevention). They are also widely used to treat hypertension, high blood pressure, although they are no longer the first choice for initial treatment of most patients. Beta blockers are competitive antagonists that block the receptor sites for the endogenous catecholamines Adrenaline, epinephrine (adrenaline) and norepinephrine (noradrenaline) on beta receptor, adrenergic beta receptors, of the sympathetic nervous system, which mediates the fight-or-flight response. Some block activation of all types of β-adrenergic receptors and others are selective for one of the three known types of beta receptors, designated β1, β2 and β3 receptors. Beta-1 adrenergic receptor, β1-adrenergic receptors are ...
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Gs Protein
The Gs alpha subunit (Gαs, Gsα) is a subunit of the heterotrimeric G protein Gs that stimulates the cAMP-dependent pathway by activating adenylyl cyclase. Gsα is a GTPase that functions as a cellular signaling protein. Gsα is the founding member of one of the four families of heterotrimeric G proteins, defined by the alpha subunits they contain: the Gαs family, Gαi/Gαo family, Gαq family, and Gα12/Gα13 family. The Gs-family has only two members: the other member is Golf, named for its predominant expression in the olfactory system. In humans, Gsα is encoded by the GNAS complex locus, while Golfα is encoded by the GNAL gene. Function The general function of Gs is to activate intracellular signaling pathways in response to activation of cell surface G protein-coupled receptors (GPCRs). GPCRs function as part of a three-component system of receptor-transducer-effector. The transducer in this system is a heterotrimeric G protein, composed of three subunits: a Gα ...
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Adenylyl Cyclase
Adenylate cyclase (EC 4.6.1.1, also commonly known as adenyl cyclase and adenylyl cyclase, abbreviated AC) is an enzyme with systematic name ATP diphosphate-lyase (cyclizing; 3′,5′-cyclic-AMP-forming). It catalyzes the following reaction: :ATP = 3′,5′-cyclic AMP + diphosphate It has key regulatory roles in essentially all cells. It is the most polyphyletic known enzyme: six distinct classes have been described, all catalyzing the same reaction but representing unrelated gene families with no known sequence or structural homology. The best known class of adenylyl cyclases is class III or AC-III (Roman numerals are used for classes). AC-III occurs widely in eukaryotes and has important roles in many human tissues. All classes of adenylyl cyclase catalyse the conversion of adenosine triphosphate (ATP) to 3',5'-cyclic AMP (cAMP) and pyrophosphate.Magnesium ions are generally required and appear to be closely involved in the enzymatic mechanism. The cAMP produced by AC ...
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Walter Bradford Cannon
Walter Bradford Cannon (October 19, 1871 – October 1, 1945) was an American physiologist, professor and chairman of the Department of Physiology at Harvard Medical School. He coined the term "fight or flight response", and developed the theory of homeostasis. He popularized his theories in his book ''The Wisdom of the Body'', first published in 1932. Life and career Cannon was born on October 19, 1871, in Prairie du Chien, Wisconsin, the son of Colbert Hanchett Cannon and his wife Wilma Denio. His sister Ida Maud Cannon (1877-1960) became a noted hospital social worker at Massachusetts General Hospital. In his autobiography ''The Way of an Investigator'', Cannon counts himself among the descendants of Jacques de Noyon, a French Canadian explorer and coureur des bois. His Calvinist family was intellectually active, including readings from James Martineau, John Fiske (philosopher), and James Freeman Clarke. Cannon's curiosity also led him to Thomas Henry Huxley, John Tyndall ...
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Beta-1 Adrenergic Receptor
The beta-1 adrenergic receptor (β1 adrenoceptor), also known as ADRB1, is a beta-adrenergic receptor, and also denotes the human gene encoding it. It is a G-protein coupled receptor associated with the Gs heterotrimeric G-protein and is expressed predominantly in cardiac tissue. Receptor Actions Actions of the β1 receptor include: The receptor is also present in the cerebral cortex. Agonists Isoprenaline has higher affinity for β1 than adrenaline, which, in turn, binds with higher affinity than noradrenaline at physiologic concentrations. Selective agonists to the beta-1 receptor are: *Denopamine *Dobutamine (in cardiogenic shock) *Xamoterol (cardiac stimulant) Antagonists ''(Beta blockers)'' β1-selective antagonists include: *Acebutolol (in hypertension, angina pectoris and arrhythmias) *Atenolol (in hypertension, coronary heart disease, arrhythmias and myocardial infarction) * Betaxolol (in hypertension and glaucoma) *Bisoprolol (in hypertension, coronary heart disea ...
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G Protein
G proteins, also known as guanine nucleotide-binding proteins, are a family of proteins that act as molecular switches inside cells, and are involved in transmitting signals from a variety of stimuli outside a cell to its interior. Their activity is regulated by factors that control their ability to bind to and hydrolyze guanosine triphosphate (GTP) to guanosine diphosphate (GDP). When they are bound to GTP, they are 'on', and, when they are bound to GDP, they are 'off'. G proteins belong to the larger group of enzymes called GTPases. There are two classes of G proteins. The first function as monomeric small GTPases (small G-proteins), while the second function as heterotrimeric G protein complexes. The latter class of complexes is made up of '' alpha'' (α), ''beta'' (β) and ''gamma'' (γ) subunits. In addition, the beta and gamma subunits can form a stable dimeric complex referred to as the beta-gamma complex . Heterotrimeric G proteins located within the cell are activ ...
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Alpha-1 Adrenergic Receptor
alpha-1 (α1) adrenergic receptors are G protein-coupled receptors (GPCRs) associated with the Gq heterotrimeric G protein. α1-adrenergic receptors are subdivided into three highly homologous subtypes, i.e., α1A-, α1B-, and α1D-adrenergic receptor subtypes. There is no α1C receptor. At one time, there was a subtype known as α1C, but it was found to be identical to the previously discovered α1A receptor subtype. To avoid confusion, naming was continued with the letter D. Catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) signal through the α1-adrenergic receptors in the central and peripheral nervous systems. The crystal structure of the α1B-adrenergic receptor subtype has been determined in complex with the inverse agonist (+)-cyclazosin. Effects The α1-adrenergic receptor has several general functions in common with the α2-adrenergic receptor, but also has specific effects of its own. α1-receptors primarily mediate smooth muscle cont ...
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