Adrenals medulla

Because duration of activity of the catecholamines is significantly longer than that of neuronally released norepinephrine, the effects on tissues are more prolonged. This difference has to do with the mechanism of inactivation of these substances. Norepinephrine is immediately removed from the neuroeffector synapse by way of reuptake into the postganglionic neuron. This rapid removal limits duration of the effect of this neurotransmitter. In 

Because catecholamines travel in the blood, organs and tissues throughout the body are exposed to them. Therefore, they are capable of stimulating tissues that are not directly innervated by sympathetic nerve fibers, hepato-cytes, and adipose tissue, in particular. As a result, the catecholamines have a much wider breadth of activity compared to norepinephrine released from sympathetic nerves. 

The third important feature distinguishing catecholamines from neu-ronally released norepinephrine involves epinephrine s affinity for -receptors. Norepinephrine has a very limited affinity for these receptors. Therefore, circulating epinephrine causes effects that differ from those of direct sympathetic innervation, including  

Epinephrine and norepinephrine have equal affinity for Pj-receptors, the predominant adrenergic receptors on the heart. However, the human heart also contains a small percentage of P2-receptors that, like Pj-receptors, are excitatory. Therefore, epinephrine is capable of stimulating a greater number of receptors and causing a greater stimulatory effect on the myocardium. 

Another noteworthy example of the relaxation of smooth muscle by way of P2-receptor stimulation involves airways. Bronchodilation, or opening of the airways, facilitates airflow in the lungs. Any direct sympathetic innervation to the lungs is irrelevant in this respect because only circulating 

The catecholamines affect most of the body s tissues by altering blood flow and energizing tissues, particularly in flght/flight responses. Within the blood, 

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C. It is secreted along with noradrenaline by the adrenal medulla, from which it may be obtained. It may be synthesized from catechol. It is used as the acid tartrate in the treatment of allergic reactions and circulatory collapse. It is included in some local anaesthetic injections in order to constrict blood vessels locally and slow the disappearance of anaesthetic from the site of injection. Ultimately it induces cellular activation of phosphorylase which promotes catabolism of glycogen to glucose. 

M.p. 103°C. Noradrenaline is released in the adrenal medulla with adrenaline, and also at the sympathetic nerve endings. Its release from a nerve fibre is followed by binding to a receptor molecule on the next nerve or muscle fibre, probably causing a change in the electrical charge of the receptor-cell membrane. Biosynthetically it normally serves as a precursor for adrenaline. 

In the anterior pituitary gland (see Hormones, anteriorpituitaryhormones), both adrenocorticotropic hormones (ACTH) and the endogenous opiate hormone, P-endorphin, are synthesized from a common prohormone (2) (see Opioids,endogenous). In the adrenal medulla, five to seven copies of another opiate hormone, methionine—enkephalin (Met-enkephalin), and one copy of leucine—enkephalin (Leu-enkephalin) are synthesized from each precursor molecule (3). 

Two AT-II receptors, AT and AT2 are known and show wide distribution (27). The AT receptor has been cloned and predominates ia regions iavolved ia the regulation of blood pressure and water and sodium retention, eg, the aorta, Hver, adrenal cortex, and ia the CNS ia the paraventricular nucleus, area postrema, and nucleus of the soHtary tract. AT2 receptors are found primarily ia the adrenal medulla, utems, and ia the brain ia the locus coeruleus and the medial geniculate nucleus. AT receptors are GCPRs inhibiting adenylate cyclase activity and stimulating phosphoHpases C, A2, and D. AT2 receptors use phosphotyrosiae phosphatase as a transduction system. 

In addition to the weU-defined opioid systems in the central nervous system, the three opioid peptides and their precursor mRNA have also been identified in peripheral tissues. ( -Endorphin is most abundant in the pituitary, where it exists in corticotroph cells with ACTH in the anterior lobe and in melanotroph cells with MSH in the intermediate lobe (59). Enkephalin and pre-pro-enkephalin mRNA have been identified in the adrenal medulla (60) and this has been the source of material for many studies of pro-enkephalin synthesis and regulation. Pre-pro-enkephalin mRNA has also been identified in the anterior and posterior lobes of the pituitary (61). mRNA for all three opioid precursors has been identified in the reproductive system (62—64). POMC... 

The chromaffin cells of the adrenal medulla may be considered to be modified sympathetic neurons that are able to synthesize E from NE by /V-methylation. In this case the amine is Hberated into the circulation, where it exerts effects similar to those of NE in addition, E exhibits effects different from those of NE, such as relaxation of lung muscle (hence its use in asthma). Small amounts of E are also found in the central nervous system, particularly in the brain stem where it may be involved in blood pressure regulation. DA, the precursor of NE, has biological activity in peripheral tissues such as the kidney, and serves as a neurotransmitter in several important pathways in the brain (1,2). 

Fig. 2. Biosynthetic pathway for epinephrine, norepinephrine, and dopamine. The enzymes cataly2ing the reaction are (1) tyrosine hydroxylase (TH), tetrahydrobiopterin and O2 are also involved (2) dopa decarboxylase (DDC) with pyridoxal phosphate (3) dopamine-P-oxidase (DBH) with ascorbate, O2 in the adrenal medulla, brain, and peripheral nerves and (4) phenethanolamine A/-methyltransferase (PNMT) with. Cadenosylmethionine in the adrenal...

Catecholamine biosynthesis begins with the uptake of the amino acid tyrosine into the sympathetic neuronal cytoplasm, and conversion to DOPA by tyrosine hydroxylase. This enzyme is highly localized to the adrenal medulla, sympathetic nerves, and central adrenergic and dopaminergic nerves. Tyrosine hydroxylase activity is subject to feedback inhibition by its products DOPA, NE, and DA, and is the rate-limiting step in catecholamine synthesis the enzyme can be blocked by the competitive inhibitor a-methyl-/)-tyrosine (31). 

Dopamine- -hydroxylase (from bovine adrenal medulla) [9013-38-1] Mr -290,000, [EC... 

Epinephrine (adrenaline). A biogenic amine released from the adrenal medulla, particularly in moments of stress. 

T No A PKA Brain (neuron), adrenal (medulla) Neurotransmission, synaptic plasticity, LTP, memory,circadian rhythm... 

Together with dopamine, adrenaline and noradrenaline belong to the endogenous catecholamines that are synthesized from the precursor amino acid tyrosine (Fig. 1). In the first biosynthetic step, tyrosine hydroxylase generates l-DOPA which is further converted to dopamine by the aromatic L-amino acid decarboxylase ( Dopa decarboxylase). Dopamine is transported from the cytosol into synaptic vesicles by a vesicular monoamine transporter. In sympathetic nerves, vesicular dopamine (3-hydroxylase generates the neurotransmitter noradrenaline. In chromaffin cells of the adrenal medulla, approximately 80% of the noradrenaline is further converted into adrenaline by the enzyme phenylethanolamine-A-methyltransferase. 

Hi-receptors in the adrenal medulla stimulates the release of the two catecholamines noradrenaline and adrenaline as well as enkephalins. In the heart, histamine produces negative inotropic effects via Hr receptor stimulation, but these are normally masked by the positive effects of H2-receptor stimulation on heart rate and force of contraction. Histamine Hi-receptors are widely distributed in human brain and highest densities are found in neocortex, hippocampus, nucleus accumbens, thalamus and posterior hypothalamus where they predominantly excite neuronal activity. Histamine Hrreceptor stimulation can also activate peripheral sensory nerve endings leading to itching and a surrounding vasodilatation ( flare ) due to an axonal reflex and the consequent release of peptide neurotransmitters from collateral nerve endings. 

Expression (Human) Tissues Leukocytes, thymus, spleen, liver, ovary Cells PBLs, neutrophils,T-cells, dendritic cells, mast cells, eosinophils, macrophages, leukocytes Tissues spleen, small intestine, placenta, lung smooth muscle, Cells bronchial smooth muscle, CD34+ hemapoietic progenitor cells, monocytes, macrophages, mast cells, eosinophils, neutrophils, PBLs, human umbilical vein endothelial cells Tissues, heart, skeletal muscle, spleen, brain, lymp node, adrenal medulla, lung, human pumonary/ saphenous vein Cells monocytes, macrophages, mast cells, eosinophils, cardiac muscle, coronary artery, PBLs... 

The main endogenous mineralocorticoid is aldosterone, which is mainly produced by the outer layer of the adrenal medulla, the zonaglomerulosa. Aldostorone, like other steroids, binds to a specific intracellular (nuclear) receptor, the mineralocorticoid receptor (MR). Its main action is to increase sodium reabsotption by an action on the distal tubules in the kidney, which is accompanied by an increased excretion of potassium and hydrogen ions. 

Pituitary Adenylyl Cyclase-activating Polypeptide (PACAP) is a 38-amino acid peptide (PACAP-38), which is widely expressed in the central nervous system. PACAP is most abundant in the hypothalamus. It is also found in the gastrointestinal tract, the adrenal gland and in testis. Its central nervous system functions are ill-defined. In the periphery, PACAP has been shown to stimulate catecholamine secretion from the adrenal medulla and to regulate secretion from the pancreas. Three G-protein coupled receptors have been shown to respond to PACAP, PAQ (PACAP type I) specifically binds PACAP, VPACi and VPAC2 also bind vasoactive intestinal peptide (VDP). Activation of PACAP receptors results in a Gs-mediated activation of adenylyl cyclase. 

Serotonin or 5-hydroxytryptamine is an important biogenic amine, which is synthesized via 5-hydroxy-tryptophan from the amino acid tryptophan. The highest concentration of serotonin occurs in the wall of the intestine. About 90% of the total amount is present in enterochromaffrn cells, which are derived from the neural crest, similarly to those of the adrenal medulla. 

VMAT1 is expressed in the adrenal medulla, by small intensely fluorescent cells in sympathetic ganglia, and by other nonneural cells that release monoamines. In contrast, VMAT2 is expressed by neuronal populations in the nervous system. The substrate specificity for the two isoforms is similar, but VMAT2 has a somewhat higher apparent affinity for all monoamines than VMAT1. In addition, only VMAT2 appears able to transport histamine, consistent with its expression by mast cells. 

N euro transmitters are chemical substances called neurohormones. These are released at Hie nerve ending that facilitate the transmission of nerve impulses. The two neurohormones (neurotransmitters) of the sympathetic nervous system are epinephrine and norepinephrine Epinephrine is secreted by the adrenal medulla Norepinephrine is secreted mainly at nerve ending of sympathetic (also called adrenergic) nerve fibers (Pig. 22-2). 

As a protective mechanism, the corticosteroids are released during periods of stress (eg, injury or surgery). The release of epinephrine or norepinephrine by the adrenal medulla during stress has a synergistic effect along with the corticosteroids. 

The small molecular transmitter characteristic of the sympathetic nervous system is norepinephrine. However, epinephrine from the adrenal medulla is an important partner in systemic sympathetic actions. The actions of the sympathetic system are unique because in different smooth muscles responses are diametrically opposed they may be either by contraction or inhibition of contraction and... 

Neural cells convert tyrosine to epinephrine and norepinephrine (Figure 31—5). While dopa is also an intermediate in the formation of melanin, different enzymes hydroxylate tyrosine in melanocytes. Dopa decarboxylase, a pyridoxai phosphate-dependent enzyme, forms dopamine. Subsequent hydroxylation by dopamine P-oxidase then forms norepinephrine. In the adrenal medulla, phenylethanolamine-A -methyltransferase uti-hzes S-adenosyhnethionine to methylate the primary amine of norepinephrine, forming epinephrine (Figure 31-5). Tyrosine is also a precursor of triiodothyronine and thyroxine (Chapter 42). 

Three amines—dopamine, norepinephrine, and epinephrine—are synthesized from tyrosine in the chromaffin cells of the adrenal medulla. The major product of the adrenal medulla is epinephrine. This compound constimtes about 80% of the catecholamines in the medulla, and it is not made in extramedullary tissue. In contrast, most of the norepinephrine present in organs innervated by sympathetic nerves is made in situ (about 80% of the total), and most of the rest is made in other nerve endings and reaches the target sites via the circu-... 

PNMT catalyzes the N-methylation of norepinephrine to form epinephrine in the epinephrine-forming cells of the adrenal medulla. Since PNMT is soluble, it is assumed that norepinephrine-to-epinephrine conversion occurs in the cytoplasm. The synthesis of PNMT is induced by glucocorticoid hormones that reach the medulla via the intra-adrenal portal system. This special system provides for a 100-fold steroid concentration gradient over systemic arterial blood, and this high intra-adrenal concentration appears to be necessary for the induction of PNMT. 

Dopamine (5-hydroxylase is a copper-containing enzyme involved in the synthesis of the catecholamines norepinephrine and epinephrine from tyrosine in the adrenal medulla and central nervous system. During hy-droxylation, the Cu+ is oxidized to Cu " reduction back... 

Proteoglycans are also found in intracellular locations such as the nucleus their function in this organelle has not been elucidated. They are present in some storage or secretory granules, such as the chromaffin granules of the adrenal medulla. It has been posm-lated that they play a role in release of the contents of such granules. The various functions of GAGs are summarized in Table 48-8. 

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