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Beta-1 Adrenergic Receptor
The beta-1 adrenergic receptor (β1 adrenoceptor), also known as ADRB1, can refer to either the protein-encoding gene (gene ADRB1) 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. Historical Context W. B. Cannon postulated that there were two chemical transmitters or sympathins while studying the sympathetic nervous system in 1933. These E and I sympathins were involved with excitatory and inhibitory responses. In 1948, Raymond Ahlquist published a manuscript in the ''American Journal of Physiology'' establishing the idea of adrenaline having distinct actions on both alpha and beta receptors. Shortly afterward, Eli Lilly Laboratories synthesized the first beta-blocker, dichloroisoproterenol. General Information Structure ADRB-1 is a transmembra ...
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Adrenergic Receptor
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 ...
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Transcription Factor
In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription (genetics), transcription of genetics, genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The function of TFs is to regulate—turn on and off—genes in order to make sure that they are Gene expression, expressed in the desired Cell (biology), cells at the right time and in the right amount throughout the life of the cell and the organism. Groups of TFs function in a coordinated fashion to direct cell division, cell growth, and cell death throughout life; cell migration and organization (body plan) during embryonic development; and intermittently in response to signals from outside the cell, such as a hormone. There are approximately 1600 TFs in the human genome. Transcription factors are members of the proteome as well as regulome. TFs work alone or with other proteins in a complex, by promoting (a ...
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Inotropic
An inotrope or inotropic is a drug or any substance that alters the force or energy of muscular contractions. Negatively inotropic agents weaken the force of muscular contractions. Positively inotropic agents increase the strength of muscular contraction. The term ''inotropic state'' is most commonly used in reference to various drugs that affect the strength of contraction of heart muscle. However, it can also refer to pathological conditions. For example, enlarged heart muscle can increase inotropic state, whereas dead heart muscle can decrease it. Medical uses Both positive and negative inotropes are used in the management of various cardiovascular conditions. The choice of agent depends largely on specific pharmacological effects of individual agents with respect to the condition. One of the most important factors affecting inotropic state is the level of calcium in the cytoplasm of the muscle cell. Positive inotropes usually increase this level, while negative inotropes ...
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Heart Atrium
The atrium (; : atria) is one of the two upper chambers in the heart that receives blood from the circulatory system. The blood in the atria is pumped into the heart ventricles through the atrioventricular mitral and tricuspid heart valves. There are two atria in the human heart – the left atrium receives blood from the pulmonary circulation, and the right atrium receives blood from the venae cavae of the systemic circulation. During the cardiac cycle, the atria receive blood while relaxed in diastole, then contract in systole to move blood to the ventricles. Each atrium is roughly cube-shaped except for an ear-shaped projection called an atrial appendage, previously known as an auricle. All animals with a closed circulatory system have at least one atrium. The atrium was formerly called the 'auricle'. That term is still used to describe this chamber in some other animals, such as the ''Mollusca''. Auricles in this modern terminology are distinguished by having thicker muscu ...
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Sinoatrial Node
The sinoatrial node (also known as the sinuatrial node, SA node, sinus node or Keith–Flack node) is an ellipse, oval shaped region of special cardiac muscle in the upper back wall of the right atrium made up of Cell (biology), cells known as pacemaker cells. The sinus node is approximately 15 millimetre, mm long, 3 mm wide, and 1 mm thick, located directly below and to the side of the superior vena cava. These cells produce an Action potential, electrical impulse known as a cardiac action potential that travels through the electrical conduction system of the heart, causing it to muscle contraction, contract. In a healthy heart, the SA node continuously produces action potentials, setting the rhythm of the heart (sinus rhythm), and so is known as the heart's cardiac pacemaker, natural pacemaker. The rate of action potentials produced (and therefore the heart rate) is influenced by the nerves that supply it. Structure The sinoatrial node is an Ellipse, oval-shaped structure that ...
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Chronotropic
Chronotropic effects (from ''chrono-'', meaning time, and ''tropos'', "a turn") are those that change the heart rate. Chronotropic drugs may change the heart rate and cardiac cycle, rhythm by affecting the electrical conduction system of the heart and the Heart#Influences, nerves that influence it, such as by changing the sinus rhythm, rhythm produced by the sinoatrial node. Positive chronotropes increase heart rate; negative chronotropes decrease heart rate. A dromotropic, dromotrope affects atrioventricular node (AV node) conduction. A positive dromotrope increases AV nodal conduction, and a negative dromotrope decreases AV nodal conduction. A Lusitropy, lusitrope is an agent that affects diastolic relaxation. Many positive inotropes affect Preload (cardiology), preload and afterload. __TOC__ Positive chronotropes * Most Adrenergic agonists * Atropine * Dopamine * Epinephrine * Isoproterenol * Milrinone * Theophylline Negative chronotropes Chronotropic variables can be consi ...
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Heart Rate
Heart rate is the frequency of the cardiac cycle, heartbeat measured by the number of contractions of the heart per minute (''beats per minute'', or bpm). The heart rate varies according to the body's Human body, physical needs, including the need to absorb oxygen and excrete carbon dioxide. It is also modulated by numerous factors, including (but not limited to) genetics, physical fitness, Psychological stress, stress or psychological status, diet, drugs, hormonal status, environment, and disease/illness, as well as the interaction between these factors. It is usually equal or close to the pulse rate measured at any peripheral point. The American Heart Association states the normal resting adult human heart rate is 60–100 bpm. An ultra-trained athlete would have a resting heart rate of 37–38 bpm. ''Tachycardia'' is a high heart rate, defined as above 100 bpm at rest. ''Bradycardia'' is a low heart rate, defined as below 60 bpm at rest. When a human sleeps, a heartbeat with ra ...
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Cardiac Muscle
Cardiac muscle (also called heart muscle or myocardium) is one of three types of vertebrate muscle tissues, the others being skeletal muscle and smooth muscle. It is an involuntary, striated muscle that constitutes the main tissue of the wall of the heart. The cardiac muscle (myocardium) forms a thick middle layer between the outer layer of the heart wall (the pericardium) and the inner layer (the endocardium), with blood supplied via the coronary circulation. It is composed of individual cardiac muscle cells joined by intercalated discs, and encased by collagen fibers and other substances that form the extracellular matrix. Cardiac muscle contracts in a similar manner to skeletal muscle, although with some important differences. Electrical stimulation in the form of a cardiac action potential triggers the release of calcium from the cell's internal calcium store, the sarcoplasmic reticulum. The rise in calcium causes the cell's myofilaments to slide past each other i ...
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Cardiac Output
In cardiac physiology, cardiac output (CO), also known as heart output and often denoted by the symbols Q, \dot Q, or \dot Q_ , edited by Catherine E. Williamson, Phillip Bennett is the volumetric flow rate of the heart's pumping output: that is, the volume of blood being pumped by a single Ventricle (heart), ventricle of the heart, per unit time (usually measured per minute). Cardiac output (CO) is the product of the heart rate (HR), i.e. the number of heartbeats per minute (bpm), and the stroke volume (SV), which is the volume of blood pumped from the left ventricle per beat; thus giving the formula: :CO = HR \times SV Values for cardiac output are usually denoted as L/min. For a healthy individual weighing 70 kg, the cardiac output at rest averages about 5 L/min; assuming a heart rate of 70 beats/min, the stroke volume would be approximately 70 mL. Because cardiac output is related to the quantity of blood delivered to various parts of the body, it is an important com ...
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Diacylglycerol
A diglyceride, or diacylglycerol (DAG), is a glyceride consisting of two fatty acid chains covalently bonded to a glycerol molecule through ester linkages. Two possible forms exist, 1,2-diacylglycerols and 1,3-diacylglycerols. Diglycerides are natural components of food fats, though minor in comparison to triglycerides. DAGs can act as surfactants and are commonly used as emulsifiers in processed foods. DAG-enriched oil (particularly 1,3-DAG) has been investigated extensively as a fat substitute due to its ability to suppress the accumulation of body fat; with total annual sales of approximately USD 200 million in Japan since its introduction in the late 1990s till 2009. Production Diglycerides are a minor component of many seed oils and are normally present at ~1–6%; or in the case of cottonseed oil as much as 10%. Industrial production is primarily achieved by a glycerolysis reaction between triglycerides and glycerol. The raw materials for this may be either vegetable oil ...
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Inositol 1,4,5-triphosphate
Inositol trisphosphate or inositol 1,4,5-trisphosphate abbreviated InsP3 or Ins3P or IP3 is an inositol phosphate signaling molecule. It is made by hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2), a phospholipid that is located in the plasma membrane, by phospholipase C (PLC). Together with diacylglycerol (DAG), IP3 is a second messenger molecule used in signal transduction in biological cells. While DAG stays inside the membrane, IP3 is soluble and diffuses through the cell, where it binds to its receptor, which is a calcium channel located in the endoplasmic reticulum. When IP3 binds its receptor, calcium is released into the cytosol, thereby activating various calcium regulated intracellular signals. Properties Chemical formula and molecular weight IP3 is an organic molecule with a molecular mass of 420.10 g/mol. Its empirical formula is C6H15O15P3. It is composed of an inositol ring with three phosphate groups bound at the 1, 4, and 5 carbon positions, and three ...
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Phosphatidylinositol 4,5-bisphosphate
Phosphatidylinositol 4,5-bisphosphate or PtdIns(4,5)''P''2, also known simply as PIP2 or PI(4,5)P2, is a minor phospholipid component of cell membranes. PtdIns(4,5)''P''2 is enriched at the plasma membrane where it is a substrate for a number of important signaling proteins. PIP2 also forms lipid clusters that sort proteins. PIP2 is formed primarily by the type I phosphatidylinositol 4-phosphate 5-kinases from PI(4)P. In metazoans, PIP2 can also be formed by type II phosphatidylinositol 5-phosphate 4-kinases from PI(5)P. The fatty acids of PIP2 are variable in different species and tissues, but the most common fatty acids are stearic in position 1 and arachidonic in 2. Signaling pathways PIP2 is a part of many cellular signaling pathways, including PIP2 cycle, PI3K signalling, and PI5P metabolism. Recently, it has been found in the nucleus with unknown function. Functions Cytoskeleton dynamics near membranes PIP2 regulates the organization, polymerization, and bra ...
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