Catecholamines epinephrine adrenaline , norepinephrine

The adrenergic receptors (or adrenoceptors) are a class of G-protein coupled receptors, which are the targets of catecholamines. Adrenergic receptors specifically bind their endogenous ligands, the catecholamines, epinephrine, and norepinephrine (also called adrenaline and noradrenaline), and are activated by these. 

Adrenal Conical Hormones. The adrenal gland is made up of two parts, the medulla and the cortex, each of which secretes characteristic hormones. The hormones of the adrenal medulla art- the catecholamines, epinephrine adrenalin and norepinephrine (noradrenalint. which are closely related chemically, dil lning only in that epinephrine has an added methyl group. See Table I. In fact, animal experiments have established a metabolic pathway lor Ihe biosynthesis of both compounds Irom Ihe ammo acid pheny lal.inine. which involves enzy malic oxidation and decarboxylation reactions It is also to he noted ihui the isomeric form of norepinephrine is most important the natural D-lonn (which incidentally, is levorntatory) has many times die uciiviiy of die synthetic isomer. Epinephrine has a pronounced action upon the circulatory system, increasing both blood... 

Chemical structures of catecholamines produced naturally in humans are shown in Figure 29-1. Epinephrine (adrenaline), norepinephrine (noradrenaline), and dopamine are phenylethylamines with hydroxylation on positions three and four of the benzene ring and with an ethylamine moiety on position one. Hydroxyl and methyl substitution on the... 

The catecholamines epinephrine and norepinephrine (adrenaline and noradrenaline) originate in the inner medullar region of the adrenal glands. Stimulation of the adrenal by the sympathetic nervous system leads to secretion of catecholamines into the bloodstream. In addition, adipose tissue is itself directly innervated by the sympathetic nervous system. Various types of metabolic stress trigger the sympathetic nervous system to release its neurotransmitter, norepinephrine, directly into adipose where its effects on the adipocyte are mediated by specific plasma membrane adrenoreceptors. Rapid reflex responses are primarily stimulated by the sympathetic nervous system, whereas more long-term (i.e., on the scale of hours, days, and weeks) and/or basal effects are subject to regulation by catecholamine secretion. 

The adrenal medulla forms part of the sympathetic nervous system and is the primary site for the production of the catecholamines—epinephrine (adrenaline) and norepinephrine (noradrenaline), which are primary hormones (also called biogenic amines). The cells of the medulla are arranged in lobules and the medulla contains chromaffin cells, which are modified postganglionic cells of the sympathetic nervous system. The medulla produces catecholamines from tyrosine and their structures contain catechol and amine groups (Figure 10.3.3). 

The sympathetic adrenal medullary (SAM) system with the secretion of the catecholamines epinephrine and norepinephrine (or adrenaline and noradrenaline) has been of particular interest in the study of stress. 

Catecholamines. The catecholamines, epinephrine (EPl adrenaline) (85), norepinephrine (NE noradrenaline) (86) (see Epinephrine and norepinephrine), and dopamine (DA) (2), are produced from tyrosine by the sequential formation of L-dopa, DA, NE, and finally EPl. EPl and NE produce their physiological effects via CC- and -adrenoceptors, a-Adrenoceptors can be further divided into CC - and a2-subtypes which in turn are divided... 

The modern usage of P2" go Asts for the treatment of asthma dates to 1903 when the effect of injected epinephrine [51-43-4] (adrenaline) C2H23NO2, (1 R = CH3) was investigated (see Epinephrine and norepinephrine) (33). As in some other modem treatments, eg, xanthines and anticholinergics, the roots of P2" go Ast therapy for asthma can be found in historical records which document the use of herbal extracts containing ephedrine [299-42-3] C qH NO, (2) as bronchodilators. Epinephrine and ephedrine are stmcturaHy related to the catecholamine norepinephrine [51-41-2] CgH NO, (1, R = H), a neurotransmitter of the adrenergic nervous system (see Neuroregulators). 

Tyrosine is also the metabolic precursor to the neurotransmitter dopamine and the catecholamine hormones norepinephrine (noradrenaline) and epinephrine (adrenaline), as well as to the alkaloids in opium, including morphine. 

The adrenal medulla synthesizes two catecholamine hormones, adrenaline (epinephrine) and noradrenaline (norepinephrine) (Figure 1.8). The ultimate biosynthetic precursor of both is the amino acid tyrosine. Subsequent to their synthesis, these hormones are stored in intracellular vesicles, and are released via exocytosis upon stimulation of the producer cells by neurons of the sympathetic nervous system. The catecholamine hormones induce their characteristic biological effects by binding to one of two classes of receptors, the a- and )S-adrenergic receptors. These receptors respond differently (often oppositely) to the catecholamines. 

Catecholamine Hormones The water-soluble compounds epinephrine (adrenaline) and norepinephrine (noradrenaline) are catecholamines, named for the structurally related compound catechol. They are synthesized from tyrosine. 

Dopamine, norepinephrine, and epinephrine (adrenalin) are biologically active amines that are collectively termed catecholamines. Dopamine and norepinephrine function as neurotransmitters in the brain and the autonomic nervous system. Norepinephrine and epinephrine are also synthesized in the adrenal medulla. 

Sites that bind adrenaline (epinephrine), noradrenaline (norepinephrine), and related catecholamines (see Chapter 30) to almost all cell surfaces are classified as either a adrenergic or (5 adrenergic receptors. The P receptors, which have been studied the most,150 occur as two major types. 

The adrenergic receptors are a class of G-protein-coupled receptor that are targets of the catecholamines, especially noradrenaline (norepinephrine) and adrenaline (epinephrine) (although dopamine is a catecholamine, its receptors are in a different category). 

In intensive care settings, sympathomimetic catecholamines [e.g., dobutamine, dopamine, epinephrine (adrenaline), isoprenaline (isoproterenol), norepinephrine (noradrenaline, and levarterenol] are often administered via continuous infusion. In clinical practice, reservoirs and administration sets of these drugs are routinely changed every 12 or 24 hours. As the pharmacological efficacy of catecholamines is directly related to their intact phenolic groups, their stability over these dosing periods is questionable. 

Cocaine (alkaloid) is used medicinally solely as a surface anaesthetic (for abuse toxicity, see p. 192) usually as a 4% solution, because adverse effects are both common and dangerous when it is injected. Even as a surface anaesthetic sufficient absorption may take place to cause serious adverse effects and cases continue to be reported only specialists should use it and the dose must be checked and restricted. Cocaine prevents the uptake of catecholamines [adrenaline (epinephrine), noradrenaline (norepinephrine)] into S5nnpathetic nerve endings, thus increasing their concentration at receptor sites, so that cocaine has a built-in vasoconstrictor action, which is why it retains a (declining) place as a... 

The catecholamine hormone epinephrine (also called adrenaline) is the fight, fright, and flight hormone. Epinephrine and the structurally similar hormone norepinephrine are released from the adrenal medulla in response to a variety of immediate stresses, including pain, hemorrhage, exercise, hypoglycemia, and hypoxia. Thus, as Ann O Rexia begins to jog, there is a rapid release of epinephrine and norepinephrine into the blood. 

What can initiate this action Catecholamines are chemicals formed from a benzene ring, adjacent hydroxyl groups, and an amine group (tyrosine). Examples are epinephrine (adrenalin), dopamine, and norepinephrine. They have specific effects on the nervous system. 

Several different types of neurotransmitter compounds are known. One is acetylcholine, and its mechanism of action seems to be best understood and will be discussed shortly. The second group called catecholamines contains rather familiar compounds such as adrenalin (epinephrine), noradrenalin (norepinephrine), and dopamine (Fig. 17.1). The third group consists of several amino acids such as regular ones glutamic acid and aspartic acid, and unusual ones such as y-aminobutyric acid (GABA) and A-methyl-D-aspartate (NMDA). Another group contains several small proteins (peptides). Examples are enkephalin, endorphin, gonadotropin, oxytocin, and vassopressin. 

These compounds, which are also called biogenic amines, are transmitters of impulses in the nervous system and in the brain. The three principal catecholamines found in the body are dopamine, norepinephrine (also called noradrenaline), and epinephrine (adrenaline). They have strong effects on body movement and balance, the emotional state, heart rate, and blood pressure. 

Tyrosine is the precursor for dihydroxyphenylala-nine (dopa), which can successively be converted to the catecholamines dopamine, noradrenaline (norepinephrine) and adrenaline (epinephrine). Although only a small proportion of tyrosine is used in this pathway, this metabolic route is extremely relevant. Dopamine is an important neurotransmitter in different parts of the brain and is involved in movement and affects pleasure and motivation. Disruption of dopamine neurons in the basal ganglia is the cause of Parkinson s disease. Noradrenaline and ardrenaline are the most important neurotransmitters in the sympathetic nervous system. The... 

As previously mentioned, the cells of the adrenal medulla are considered modified sympathetic postganglionic neurons. Instead of a neurotransmitter, these cells release hormones into the blood. Approximately 20% of the hormonal output of the adrenal medulla is norepinephrine. The remaining 80% is epinephrine (EPI). Unlike true postganglionic neurons in the sympathetic system, the adrenal medulla contains an enzyme that methylates norepinephrine to form epinephrine. The synthesis of epinephrine, also known as adrenalin, is enhanced under conditions of stress. These two hormones released by the adrenal medulla are collectively referred to as the catecholamines. 

Amino acid derivatives include the thyroid hormones, catecholamines (e.g. adrenaline (epinephrine)) and dopamine, neurotransmitters such as y-aminobutyric acid (GABA) and noradrenaline (norepinephrine). All of these signalling molecules retain... 

Two amino acids, tyrosine and arginine are of particular importance as precursors of signalling molecules. As outlined in Figure 4.3, tyrosine is the amino acid precursor of thyroid hormones tri-iodothyronine (T3) and tetra-iodothyronine (T4) and also of catecholamines adrenaline (epinephrine) and noradrenaline (norepinephrine). 

Known most famously for their part in the fight or flight response to a threat, challenge or anger, adrenaline (epinephrine) and dopamine from the adrenal medulla and noradrenaline (norepinephrine), mainly from neurones in the sympathetic nervous system are known collectively as catecholamines. Synthesis follows a relatively simple pathway starting with tyrosine (Figure 4.7). 

The first step is catalysed by the tetrahydrobiopterin-dependent enzyme tyrosine hydroxylase (tyrosine 3-monooxygenase), which is regulated by end-product feedback is the rate controlling step in this pathway. A second hydroxylation reaction, that of dopamine to noradrenaline (norepinephrine) (dopamine [3 oxygenase) requires ascorbate (vitamin C). The final reaction is the conversion of noradrenaline (norepinephrine) to adrenaline (epinephrine). This is a methylation step catalysed by phenylethanolamine-jV-methyl transferase (PNMT) in which S-adenosylmethionine (SAM) acts as the methyl group donor. Contrast this with catechol-O-methyl transferase (COMT) which takes part in catecholamine degradation (Section 4.6). 

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