|Died||December 25, 1961 88) (aged|
|Nationality||Austria, Germany, United States|
|Alma mater||University of Strasbourg|
|Spouse(s)||Guida Goldschmiedt (m. 1908; 4 children) (1889-1958)|
Otto Loewi (German: [ˈɔtoː ˈløːvi] ( listen ); 3 June 1873 – 25 December 1961) was a German-born pharmacologist and psychobiologist who discovered the role of acetylcholine as an endogenous neurotransmitter. For his discovery he was awarded the Nobel Prize in Physiology or Medicine in 1936, which he shared with Sir Henry Dale, who was a lifelong friend that helped to inspire the neurotransmitter experiment. Loewi met Dale in 1902 when spending some months in Ernest Starling's laboratory at University College, London.
Loewi was born in Frankfurt, Germany on June 3, 1873 in a Jewish family. He went to study medicine at the University of Strasbourg , Germany (Now part of France) in 1891, where he attended courses by famous professors Gustav Schwalbe, Oswald Schmiedeberg, and Bernhard Naunyn among others. He received his medical doctoral degree in 1896. He also was a member of the fraternity Burschenschaft Germania Strassburg.
Subsequently, he worked with Martin Freund at Goethe University of Frankfurt and with Franz Hofmeister in Strasbourg.From 1897 to 1898, he served as an assistant to Carl von Noorden, clinician at the City Hospital in Frankfurt. Soon, however, after seeing the high mortality in countless cases of far-advanced tuberculosis and pneumonia, left without any treatment because of lack of therapy, he decided to drop his intention to become a clinician and instead to carry out research in basic medical science, in particular pharmacology. In 1898, he became an assistant of Professor Hans Horst Meyer, the renowned pharmacologist at the University of Marburg. During his first years in Marburg, Loewi's studies were in the field of metabolism. As a result of his work on the action of phlorhizin, a glucoside provoking glycosuria, and another one on nuclein metabolism in man, he was appointed «Privatdozent» (Lecturer) in 1900. Two years later he published his paper «Über Eiweisssynthese im Tierkörper» (On protein synthesis in the animal body), proving that animals are able to rebuild their proteins from their degradation products, the amino acids – an essential discovery with regard to nutrition.
In 1902 Loewi was a guest researcher in Ernest Starling's laboratory in London, where he met his lifelong friend Henry Dale.
In 1903, he accepted an appointment at the University of Graz in Austria, where he would remain until being forced out of the country in 1938. In 1905, Loewi became Associate Professor at Meyer's laboratory and received Austrian citizenship. In 1909 he was appointed to the Chair of Pharmacology in Graz.
He married Guida Goldschmiedt (1889-1958) in 1908. They had three sons and a daughter. He was the last Jew hired by the University between 1903 and the end of the war.
In 1921, Loewi investigated how vital organs respond to chemical and electrical stimulation. He also established their relative dependence on epinephrine for proper function. Consequently, he learnt how nerve impulses are transmitted by chemical messengers. The first chemical neurotransmitter that he identified was acetylcholine.
After being arrested, along with two of his sons, on the night of the German invasion of Austria, March 11, 1938, Loewi was released after three months on condition that he "voluntarily" relinquish all his possessions, including his research, to the Nazis. He went initially to Britain and shortly afterwards the he was offered a visiting professorship at the Université libre de Bruxelles via the Francqui Foundation.Loewi moved to the United States in 1940, where he became a research professor at the New York University College of Medicine. In 1946, he became a naturalized citizen of the United States. In 1954, he became a Foreign Member of the Royal Society. He died in New York City on December 25, 1961.
Shortly after Loewi's death in late 1961, his youngest son bestowed the gold Nobel medal on the Royal Society in London. He gave the Nobel diploma to the University of Graz in Austria in 1983, where it currently resides, along with a bronze copy of a bust of Loewi. The original of the bust is at the Marine Biological Laboratory in Woods Hole, Massachusetts, Loewi's summer home from his arrival in the US until his death.
Before Loewi's experiments, it was unclear whether signaling across the synapse was bioelectrical or chemical. While pharmacology experiments had established that physiological responses such as muscle contraction could be induced by chemical application, there was no evidence that cells released chemical substances to cause these responses.On the contrary, researchers had shown that physiological responses could be caused by applying an electrical impulse, which suggested that electrical transmission may be the only mode of endogenous signaling. In the early 20th century the controversy of whether cells used chemical or electrical transmission divided even the most prominent scientists.
Loewi's famous experiment, published in 1921, largely answered this question. He dissected out of frogs two beating hearts: one with the vagus nerve which controls heart rate attached, the other heart on its own. Both hearts were bathed in a saline solution (i.e. Ringer's solution). By electrically stimulating the vagus nerve, Loewi made the first heart beat slower. Then, Loewi took some of the liquid bathing the first heart and applied it to the second heart. The application of the liquid made the second heart also beat slower, proving that some soluble chemical released by the vagus nerve was controlling the heart rate. He called the unknown chemical Vagusstoff, naming it after the nerve and the German word for substance. It was later found that this chemical corresponded to acetylcholine. His experiment was iconic because it was the first to demonstrate the endogenous release of a chemical substance that could cause a response in the absence of electrical stimulation. It paved the way for the understanding that the electrical signaling event (action potential) causes a chemical event (release of neurotransmitter from synapses) that is ultimately the effector on the tissue.
Loewi's investigations "On an augmentation of adrenaline release by cocaine" and "On the connection between digitalis and the action of calcium" stimulated a considerable body of research in the years following their publication.
He also clarified two mechanisms of therapeutic importance: the blockade and the augmentation of nerve action by certain drugs.
Loewi is also known for the means by which the idea for his experiment came to him. On Easter Saturday 1921, he dreamed of an experiment that would prove once and for all that transmission of nerve impulses was chemical, not electrical. He woke up, scribbled the experiment onto a scrap of paper on his night-stand, and went back to sleep.
The next morning, he found, to his horror, that he couldn't read his midnight scribbles. That day, he said, was the longest day of his life, as he could not remember his dream. That night, however, he had the same dream. This time, he immediately went to his lab to perform the experiment.From that point on, the consensus was that the Nobel was not a matter of "if" but of "when."
Thirteen years later, Loewi was awarded the Nobel Prize in Physiology or Medicine, which he shared with Sir Henry Hallett Dale.
Loewi observed the removing the pancreas from dogs, giving them an experimental form of diabetes led a change of the response of the eye to adrenaline: this compound in normal dogs has no effect, but in the dogs without a pancreas the pupil dilated.This test involves instilling repeated doses of 1:1000 adrenaline solution into the eye and looking for pupillary dilation. Surgeons used this as a diagnostic test for acute pancreatitis, which was based on Loewi's observation of such a phenomenon in dogs that had had their pancreas removed. The usefulness of this test was reported in a case series of two patients; it was, as expected, negative in a case involving carcinoma of the bile duct, but positive in a case of pancreatitis. The effectiveness of this test was subsequently investigated. The mechanism of action of this phenomenon is unclear, but has been attributed to "probably due to a functional toxic disturbance of the sympathetic post-ganglionic neuron innervating the iris".
Endocrinology is a branch of biology and medicine dealing with the endocrine system, its diseases, and its specific secretions known as hormones. It is also concerned with the integration of developmental events proliferation, growth, and differentiation, and the psychological or behavioral activities of metabolism, growth and development, tissue function, sleep, digestion, respiration, excretion, mood, stress, lactation, movement, reproduction, and sensory perception caused by hormones. Specializations include behavioral endocrinology and comparative endocrinology.
Neurotransmitters are chemical messengers that transmit a signal from a neuron across the synapse to a target cell, which can be a different neuron, muscle cell, or gland cell. Neurotransmitters are chemical substances made by the neuron specifically to transmit a message.
The vagus nerve, historically cited as the pneumogastric nerve, is the tenth cranial nerve or CN X, and interfaces with the parasympathetic control of the heart, lungs, and digestive tract. The vagus nerves are normally referred to in the singular. It is the longest nerve of the autonomic nervous system in the human body and comprises sensory and motor fibers. The sensory fibers originate from neurons of the nodose ganglion, whereas the motor fibers come from neurons of the dorsal motor nucleus of the vagus and the nucleus ambiguus.
Acetylcholine (ACh) is an organic chemical that functions in the brain and body of many types of animals as a neurotransmitter—a chemical message released by nerve cells to send signals to other cells, such as neurons, muscle cells and gland cells. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Parts in the body that use or are affected by acetylcholine are referred to as cholinergic. Substances that increase or decrease the overall activity of the cholinergic system are called cholinergics and anticholinergics, respectively.
The autonomic nervous system (ANS), formerly the vegetative nervous system, is a division of the peripheral nervous system that supplies smooth muscle and glands, and thus influences the function of internal organs. The autonomic nervous system is a control system that acts largely unconsciously and regulates bodily functions, such as the heart rate, digestion, respiratory rate, pupillary response, urination, and sexual arousal. This system is the primary mechanism in control of the fight-or-flight response.
Sir Bernard Katz, FRS was a German-born British physician and biophysicist, noted for his work on nerve physiology. He shared the Nobel Prize in physiology or medicine in 1970 with Julius Axelrod and Ulf von Euler. He was made a Knight Bachelor in 1969.
Sir Henry Hallett Dale was an English pharmacologist and physiologist. For his study of acetylcholine as agent in the chemical transmission of nerve pulses (neurotransmission) he shared the 1936 Nobel Prize in Physiology or Medicine with Otto Loewi.
Carl Ferdinand Cori, ForMemRS was a Czech-American biochemist and pharmacologist born in Prague who, together with his wife Gerty Cori and Argentine physiologist Bernardo Houssay, received a Nobel Prize in 1947 for their discovery of how glycogen – a derivative of glucose – is broken down and resynthesized in the body, for use as a store and source of energy. In 2004, both were designated a National Historic Chemical Landmark in recognition of their work that elucidated carbohydrate metabolism.
Julius Axelrod was an American biochemist. He won a share of the Nobel Prize in Physiology or Medicine in 1970 along with Bernard Katz and Ulf von Euler. The Nobel Committee honored him for his work on the release and reuptake of catecholamine neurotransmitters, a class of chemicals in the brain that include epinephrine, norepinephrine, and, as was later discovered, dopamine. Axelrod also made major contributions to the understanding of the pineal gland and how it is regulated during the sleep-wake cycle.
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Ulf Svante von Euler was a Swedish physiologist and pharmacologist. He shared the Nobel Prize in Physiology or Medicine in 1970 for his work on neurotransmitters.
Herbert Spencer Gasser was an American physiologist, and recipient of the Nobel Prize for Physiology or Medicine in 1944 for his work with action potentials in nerve fibers while on the faculty of Washington University in St. Louis, awarded jointly with Joseph Erlanger.
In neuroscience, Dale's principle is a rule attributed to the English neuroscientist Henry Hallett Dale. The principle basically states that a neuron performs the same chemical action at all of its synaptic connections to other cells, regardless of the identity of the target cell. However, there has been disagreement about the precise wording.
Vagusstoff refers to the substance released by stimulation of the vagus nerve which causes a reduction in the heart rate. Discovered in 1921 by physiologist Otto Loewi, vagusstoff was the first confirmation of chemical synaptic transmission and the first neurotransmitter ever discovered. It was later confirmed to be acetylcholine, which was first identified by Sir Henry Hallett Dale in 1914. Because of his pioneering experiments, in 1936 Loewi was awarded the Nobel Prize in Physiology or Medicine, which he shared with Dale.
From the ancient Egyptian mummifications to 18th-century scientific research on "globules" and neurons, there is evidence of neuroscience practice throughout the early periods of history. The early civilizations lacked adequate means to obtain knowledge about the human brain. Their assumptions about the inner workings of the mind, therefore, were not accurate. Early views on the function of the brain regarded it to be a form of "cranial stuffing" of sorts. In ancient Egypt, from the late Middle Kingdom onwards, in preparation for mummification, the brain was regularly removed, for it was the heart that was assumed to be the seat of intelligence. According to Herodotus, during the first step of mummification: "The most perfect practice is to extract as much of the brain as possible with an iron hook, and what the hook cannot reach is mixed with drugs." Over the next five thousand years, this view came to be reversed; the brain is now known to be the seat of intelligence, although colloquial variations of the former remain as in "memorizing something by heart".
Marthe Louise Vogt was a German scientist recognized as one of the leading neuroscientists of the twentieth century. She is mainly remembered for her important contributions to the understanding of the role of neurotransmitters in the brain, especially epinephrine.
UCL Neuroscience is a research domain that encompasses the breadth of neuroscience research activity across University College London's (UCL) School of Life and Medical Sciences. The domain was established in January 2008, to coordinate neuroscience activity across the many UCL departments and institutes in which neuroscience research takes place. In 2014, the Nobel Prize in Physiology or Medicine was awarded to the UCL neuroscientist John O'Keefe. In two consecutive years 2017 and 2018, the Brain Prize, the world's most valuable prize for brain research at €1m, was awarded to UCL neuroscientists Peter Dayan, Ray Dolan, John Hardy, and Bart De Strooper.
Autopharmacology relates to the scientific study of the regulation of body functions by the activity of its naturally existent chemical factors of the tissues. A more restricted definition would consider substances that were first identified as external agents which had a documented action on physiological functions, but later were discovered as existing as endogenous factors. The best example is the class of endorphins, which, as its name implies, were discovered to exist in the brain and have specific receptors in it, by investigations on the mechanism of action of opioids, such as morphine.
The catecholamines comprise the endogenous substances dopamine, noradrenaline (norepinephrine) and adrenaline (epinephrine) as well as numerous artificially synthesized compounds such as isoprenaline. Their investigation constitutes a prominent chapter in the history of physiology, biochemistry and pharmacology. Adrenaline was the first hormone extracted from its endocrine gland and obtained in pure form, before the word hormone was coined. It was also the first hormone the structure and biosynthesis of which were clarified. Apart from acetylcholine, adrenaline and noradrenaline were the first neurotransmitters to be discovered and the first intercellular biochemical signals to be found in intracellular vesicles. The β-adrenoceptor was the first G protein-coupled receptor the gene of which was cloned. Goal-directed catecholamine research began with the preparation by George Oliver and Edward Albert Sharpey-Schafer of a pharmacologically active extract from the adrenal glands.
An organ chamber, organ bath, or isolated tissue bath is a chamber in which isolated organs or tissues can be administered with drugs, or stimulated electrically, in order to measure their function. The tissue in the organ bath is typically oxygenated with carbogen and kept in a solution such as Tyrode's solution or lactated Ringer's solution. Historically, they have also been called gut baths.