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Epinephrine

Epinephrine

Epinephrine, also known as adrenaline, is a hormone secreted by the medulla (inner part) of the adrenal glands, located on the kidneys. The adrenal glands are one of the body's endocrine glands (glands producing substances that are distributed by way of the bloodstream).

Epinephrine was the first hormone to be discovered. Hormones are substances produced by body cells that circulate in body fluid and influence the activity of cells in another part of the body. In the 1950s, the American pharmacologist Earl Sutherland (1915-1974) discovered that epinephrine does not act directly on cells, but stimulates production of cyclic AMP, a second messenger that regulates cell activity.

Epinephrine is produced continuously in small amounts by the adrenal glands, but when the body is threatened in times of excitement, danger, or emotional stress, the brain sends messages to the adrenal glands, which respond by increasing epinephrine production.

This increase in epinephrine stimulates the heart, raises blood pressure, constricts small blood vessels, releases sugar stored in the liver, and relaxes certain involuntary muscles while it contracts others. These changes in the body prepare it for "fight or flight," meaning the body is more alert, physically stronger, and has greater energy. The person is now better prepared to face the danger at hand (fight) or escape from the danger or stress (flight).

Early Research and Use

The power of adrenal extracts was first observed by the British physiologist Edward Sharpey-Schafer (1850-1935). In 1894 he injected an adrenal extract into an experimental animal, causing its blood vessels to narrow and forcing an increase in blood pressure. Japanese American chemist Jokichi Takemine (1854-1922) isolated epinephrine in 1901, based on preliminary work done in 1897 by American pharmacologist John Jacob Abel (1857-1938).

Epinephrine was soon available for medical purposes such as reviving persons suffering from hemorrhage and shock. It was once prepared using adrenal glands of animals, but is now produced synthetically.

Hormones and the Body

In 1905 the British physiologists William Bayliss (1860-1924) and Ernest Starling (1866-1927) introduced the concept of a hormone, a sub-stance that is produced by one organ and carried by the blood to another organ, where it influences its functions. Only then did scientists realize that epinephrine was a hormone.

The significance of epinephrine and other hormones in the body's operations was discovered by the American physiologist Walter Bradford Cannon (1871-1945), after he worked with injured World War I (1914-1918) soldiers. Other scientists had already studied the body as an internal environment and the interrelation of metabolism, hormones, and the immune system. In 1926 Cannon developed the concept of homeostasis (an organism's ability to remain stable internally, even when the surrounding environment exerts great stress upon it, such as hunger, thirst, and sudden danger). Homeostasis in turn led to such ideas as biofeedback (the interaction of internal and external signals and responses in the body).

Catecholamines

Epinephrine is one of several structurally related compounds in the body called catecholamines. These compounds help regulate the sympathetic nervous system, which is part of the autonomic nervous system. The autonomic nervous system helps the body maintain homeostasis. The autonomic nervous system makes rapid adjustments to changes in environment by freeing chemical agents that act as they are released.

The endocrine system acts more slowly by releasing agents over periods of hours or days. Because it releases hormones but acts so quickly, the adrenal medulla cannot be strictly classified as part of the nervous system or part of the endocrine system. The neurohumoral theory may explain how the two act as one in many cases.

Other catecholamines are norepinephrine (also called noradrenaline or levoarterenol) and dopamine. The general function of norepinephrine seems to be the maintenance of normal blood circulation. It is also the chemical agent that is responsible for transmission of nerve impulses in the sympathetic nervous system. When a person has certain tumors of the adrenal glands, large amounts of epinephrine and norepinephrine are produced, causing a great increase in blood pressure. Dopamine is also a nerve impulse transmitter.

Synthetic (synthesized) catecholamines are important in medicine as heart stimulants and vasoconstrictors (substances that cause blood vessels to narrow), as well as relaxants of the bronchial and other muscles.

Vasopressors

Epinephrine is one of the most powerful vasopressor (causing a rise in blood pressure) drugs known. It increases the strength of heart muscle contractions as well as the heart rate, and it constricts blood vessels and veins. Because it is a powerful heart stimulant, it is used in emergency medicine to restore heart rhythm in cases of shock and in certain cases of cardiac arrest (heart attack). The most common use of epinephrine in medicine is to relieve breathing distress in patients with asthma, bronchitis, and emphysema. The synthetic catecholamine isoproterenol is also used in the treatment of these diseases.

Epinephrine is a powerful bronchodilator, meaning it relaxes bronchial muscle. It also constricts pulmonary vessels (in the lung), and inhibits the release of histamines triggered by allergic reactions. As a bronchodilator it is most often inhaled by mouth as a spray or through another breathing apparatus. Epinephrine is also used on the skin or mucous membranes to control bleeding of wounds because it constricts blood vessels. It is sometimes used for the same reason during surgery of the nose, throat, and larynx, where it also shrinks mucosa (membranes that secrete slime), making surgery easier.

Epinephrine increases metabolism, accelerates blood coagulation, and lowers pressure inside the eye in some types of glaucoma.

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Epinephrine

Epinephrine


Epinephrine, also known as adrenalin , is a hormone that is responsible for the "fight or flight" reaction in mammals. Chemically, it mobilizes the body's defense system, inducing the release into the blood of large amounts of glucose from stores in the liver and muscles. This burst of energy is the familiar "adrenalin rush" one experiences when frightened or excited. In some tissues, epinephrine also acts as a neurotransmitter, conveying signals between adjacent nerve cells.

Epinephrine (see Figure 1) is synthesized in several steps from either phenylalanine or tyrosine (both amino acids). Two adjacent hydroxyl groups are placed on the aromatic ring, leading to the ring structure called catechol. These hydroxylations form the intermediate L-dopa, which in turn is converted to dopamine (a neurotransmitter), norepinephrine (also a neurotransmitter), and finally epinephrine. Epinephrine together with norepinephrine and dopamine make up the family of biogenic amines called catecholamines.

Nerve signals to the adrenal gland activate the conversion of stores of norepinephrine to epinephrine and its release into the bloodstream. The fight or flight reaction includes increased blood glucose, increased vasoconstriction in certain parts of the body, and increased heart rate. At the cellular level, epinephrine binds to liver and muscle cells at specific receptors on the outside surface of cell membranes. Such a receptor then activates a series of enzymatic reactions inside the cell, culminating in the synthesis of large amounts of cyclic adenosine monophosphate (cAMP). Epinephrine cannot cross the cell membrane, so its hormonal signal is transmitted inside the cell via cAMP, acting as a second messenger (epinephrine being the first messenger). CyclicAMP switches on a cascade of enzymesmostly kinases that place a phosphate group at specific sites on other proteins or enzymes. These phosphorylations serve to activate (or in some cases inhibit) enzymatic reactions. The end result is the activation of glycogen phosphorylase, an enzyme that breaks down glycogen into its glucose units, and the release of glucose into the bloodstream.

The neurotransmitter action of epinephrine is terminated by reuptake into the neuron that released it, or breakdown to inactive metabolites by the enzymes catechol-O-methyl transferase (COMT) and monoamine oxidase (MAO). The second messenger effects inside the cell are terminated by enzymes that break down cAMP, and by phosphatases that reverse the action of the kinases by removing phosphates.

Epinephrine also acts at a crucial regulatory step in the synthesis of fatty acids. The activity of the first enzyme in fatty acid synthesis, acetyl-coenzyme A (AcCoA) carboxylase, is regulated by phosphorylation . The phosphorylated enzyme is inactive (and subsequent fatty acid synthesis is halted), whereas the dephosphorylated enzyme is active. Epinephrine, through the second messenger cAMP, prevents the dephosphorylation of AcCoA carboxylase, rendering it inactive and halting the synthesis of fatty acids. Indeed, during the fight or flight reaction, the organism needs to release energy in the form of glucose and fatty acids rather than store energy as glycogen or fat.

Clinically, epinephrine plays a lifesaving role in countering the effects of anaphylactic shock. Histamines released in large amounts upon the body's exposure to an allergen (bee stings in certain individuals, for instance) can constrict smooth muscle, including that in the airway passages. Epinephrine does the opposite: It relaxes smooth muscle, though at different receptors. Its effects on heart muscle (increasing the heart rate) can be used as a life-saving measure when a patient's heart has stopped. Epinephrine is also used in conjunction with local anesthetics such as lidocaine. By constricting blood vessels near the site of the injection, it keeps the anesthetic from diffusing away from the site.

see also Kinase.

C. Larry Bering

Bibliography

Devlin, Thomas M., ed. (2002). Textbook of Biochemistry: With Clinical Correlations, 5th edition. New York: Wiley-Liss.

Marieb, Elaine N. (2001). Human Anatomy and Physiology, 5th edition. New York: Addison Wesley Longman.

Voet, Donald, and Voet, Judith G. (1995). Biochemistry, 2nd edition. New York: Wiley.

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epinephrine

epinephrine (ĕp´ənĕf´rīn), hormone important to the body's metabolism, also known as adrenaline. Epinephrine, a catecholamine, together with norepinephrine, is secreted principally by the medulla of the adrenal gland. Heightened secretion caused perhaps by fear or anger, will result in increased heart rate and the hydrolysis of glycogen to glucose. This reaction, often called the "fight or flight" response, prepares the body for strenuous activity. The hormone was first extracted (1901) from the adrenal glands of animals by Jokichi Takamine; it was synthesized (1904) by Friedrich Stolz. Epinephrine is used medicinally as a stimulant in cardiac arrest, as a vasoconstrictor in shock, as a bronchodilator and antispasmodic in bronchial asthma, and to lower intra-ocular pressure in the treatment of glaucoma.

See B. B. Hoffman, Adrenaline (2013).

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epinephrine

ep·i·neph·rine / ˌepiˈnefrin/ • n. Biochem. a hormone secreted by the adrenal glands, esp. in conditions of stress, increasing rates of blood circulation, breathing, and carbohydrate metabolism and preparing muscles for exertion. Also called adrenaline.

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epinephrine

epinephrine (epi-nef-rin) n. see adrenaline.

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epinephrine

epinephrine See adrenaline.

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epinephrine

epinephrine See adrenaline.

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epinephrine

epinephrine See ADRENALIN.

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epinephrine

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