Chromaffin tissue

The arylamino acid decarboxylase inhibitory action of DL-a-fluoromethyldopa (4.77) has also been described. By affecting the enzyme through covalent binding, this compound completely inhibits both catecholamine and serotonin synthesis. Unlike 6-hydroxydopamine, a-fluoromethyldopa does not destroy the neurons, and unlike reserpine it does not deplete chromaffin tissue in the adrenal gland. 

Paradoxically, elevated levels of E and NE can cause a reduction in plasma volume that can lead to hemoconcen-tration and poor tissue perfusion however, the mechanism of this effect is not known. This is said to be the cause of orthostatic hypotension in untreated patients with pheochro-mocytoma, a tumor of chromaffin tissue that produces excessive amounts of NE most of these patients have reduced plasma volume but exhibit hypertension while in the reclining position. 

The adrenal medulla and other chromaffin tissue are embryologically and anatomically similar to sympathetic ganglia. The adrenal medulla differs from sympathetic ganglia in that its principal catecholamine is epinephrine (Epi, adrenaline), notNE. The chromaffin cells in the adrenal medulla are innervated by typical preganglionic fibers that release ACh. 

SYNTHESIS, STORAGE, AND RELEASE OF CATECHOLAMINES Synthesis—The steps in the synthesis of DA, NE (known outside the U.S. as noradrenaline), and Epi (known as adrenahne) are shown in Eigure 6-A. Tyrosine is sequentially 3-hydroxylated and decarboxylated to form DA. DA is 3-hydroxylated to yield NE (the transmitter in postganglionic nerves of the sympathetic branch of the ANS), which is N-methylated in chromaffin tissue to give Epi. The enzymes involved are not completely specific consequently, other endogenous substances and some drugs are also substrates. 5-hydroxytryptamine (5-HT, serotonin) can be produced from 5-hydroxy-L-tryptophan by aromatic L-amino acid decarboxylase (AAD or dopa decarboxylase). AAD also converts dopa into DA, and methyldopa to a-methyl-DA, which is converted to a-methyl-NE by dopamine /3-hydroxylase (Dj3H Table 6-4). 

A well encapsulated, lobular, vascular tumour of chromaffin tissue of the adrenal medulla or sympathetic paraganglia. 

The Zuckerkandl organs arc para-aortic bodies of chromaffin tissue, which arc located retroperitoneally at the, level of the origin of the inferior mesenteric artery. These organs function as an accessory tissue to the autonomic nervous system in early life they usually start to degenerate during the first postnatal year. 

The molar proportion of catecholamines to adenosine triphosphate in the medulla of the normal human suprarenal gland is about 1 4-5, whereas in tissue from a phaeochromocytoma a proportion of 1 10-35 was found. This observation, coupled with that of decreased granular storage of catecholamines in the cells of a phaeochromocytoma, point to a disturbance in the storage mechanisms of cells from chromaffine tissue tumours. (989,1469) increased secretion from such tumours is probably connected with this disturbance. 

The phaeochromocytoma and the paraganglioma are tumours of the chromaffine tissue (chromaffinomata). The former originates from the suprarenal medulla, the latter from chromaffine cells which are outside the suprarenal gland. The local distribution of these tumours is summarized in Table which is based on observations in 204 patients with a... 

Tumours of chromaffin tissue (phaeochromocytoma). These are mainly adrenal tumours. 

A catecholamine secreting tumour of chromaffin tissue occuring mainly in adults. The majority of these tumours are located in... 

The morphology of the carotid body resembles chromaffin tissues expressing catecholamines. Now it is fairly established that carotid bodies express dopamine and norepinephrine, whereas there is no convincing evidence for epinephrine. Type I cells from a variety of species express tyrosine hydroxylase (TH) and dopamine jS hydroxylase (DBH), the enzymes responsible for the synthesis of dopamine (DA) and norepinephrine (NE), respectively (10,20,91). In addition, nerve fibers (of sensory as well as autonomic origin) and ganghon cells also show TH immunoreactivity (91). The actions of DA and NE are terminated by a reuptake mechanism involving specific transporters. However, evidence for DA and/or NE transporters in the carotid body is lacking. 

Both hormones are pyrocatechol (o-dihydroxybenzene) derivatives, which are easily oxidized. This fact explains the histochemical reaction of the chromaffin tissue. The hormonal content of the adrenal medulla is relatively high (several mg per gm of gland). The two active substances of the adrenal medulla, epinephrine and norepinephrine, are both derivatives of phenyl ethylamine, which possesses strong pharmacologic effects. 

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). 

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-... 

Winkler, H (1993) The adrenal chromaffin granule a model for larger dense core vesicles of endocrine and nervous tissue. J. Anat. 183 237-252. 

As might be expected, mRNA for the 5-HT transporter is found in high concentrations in the Raphe nuclei but it is also found in other brain regions. Whether this means that non-5-HT neurons can synthesise this protein is unknown but there is some evidence that it is synthesised in astrocytes, at least. One complication is that there are multiple forms of mRNA for the 5-HT transporter, but there is, as yet, no evidence for transporter subtypes in the CNS. However, it must also be remembered that 5-HT transporters are found in the peripheral tissues, notably platelets, mast cells, the placental brush-border and adrenal chromaffin cells and it is possible that these are not all identical. 

Vertebrates also show expression of AADC in both neural and non-neural tissues. AADC has been purified from kidney (Christenson et al., 1972), liver (Ando-Yamamoto et al., 1987), adrenal medulla (Albert et al., 1987), and pheochromocytoma (Coge et al., 1989 Ichinose et al., 1989). In the adrenal medulla dopamine is further processed into epinephrine and norepinephrine, which are released from the chromaffin cells during stress to increase heart rate and blood pressure. There are no detectable monoamines in the liver and kidney, and the function of AADC in these tissues is unknown. AADC activity has also been... 

Several types of cells related to sympathetic neurons can be maintained and studied in tissue culture. Adrenal medullary chromaffin cells have the same precursor cells... 

Adrenaline is the main hormone released from the adrenal medulla. The glandular cells in this structure correspond to the second, postganglionic neuron of the sympathetic nervous system. Furthermore, adrenaline can be found in chromaffin cells in various tissues. For the better understanding of the function of noradrenaline it is important to realize that this substance, as a neuronal transmitter, affects only the innervated target structure, that is it acts mainly locally. Among these effects are the activation of the musculus dilatator to widen the pupillae in response to a reduced light intensity, an increase in heart rate as a response to a blood pressure drop due to a reduction of the peripheral resistance or constriction... 

Diverse-Pierluissi M, Dunlap K, Westhead EW (1991) Multiple actions of extracellular ATP on calcium currents in cultured bovine chromaffin cells. Proc Natl Acad Sci USA 88 1261-5 Dixon AK, Gubitz AK, Sirinathsinghji DJ et al (1996) Tissue distribution of adenosine receptor mRNAs in the rat. Br J Pharmacol 118 1461-8... 

Today, with the exception of bone marrow for hematopoietic reconstitution, therapeutic cellular transplantation is an emerging technology. In recent years novel approaches in the potential restoration of function through cellular transplantation have included the use of fetal human or xenogeneic neural tissue for Parkinson s disease, ectopically implanted pancreatic islets for diabetes, Schwann cells and olfactory ensheathing glia for spinal cord injury, encapsulated chromaffin cells for pain, and various types of stem cells for the treatment of diabetes, cardiac disease, and central nervous system injuries or disease [2], There have also been trials of encapsulated cells to provide enzymes that either remove toxic products or provide activation of prodrugs to therapeutics, usually anticancer derivatives. 

The protein systems used in these chromaffin vesicles, which represent dense core secretory vesicles (71), resemble those of brain synaptic vesicles (88) and secretory vesicles in the liver (89). Proteomic studies provide inference for secretory vesicle protein systems used for functions of these vesicles, including their biogenesis, that are required for production of enkephalin and related neuropeptides in brain and endocrine tissues. 

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