Adrenal chromaffin cells

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). 

Adrenaline (epinephrine) is a catecholamine, which is released as a neurotransmitter from neurons in the central nervous system and as a hormone from chromaffin cells of the adrenal gland. Adrenaline is required for increased metabolic and cardiovascular demand during stress. Its cellular actions are mediated via plasma membrane bound G-protein-coupled receptors. 

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. 

Liu PS, Kao LS, Lin MK. 1994. Organophosphates inhibit catecholamine secretion and calcium influx in bovine adrenal chromaffin cell. Toxicology 90 81-91. 

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-... 

Figure 4. Effect of pardaxin on intracellular ionized calcium level in bovine adrenal chromaffin cells.

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. 

Non-neuronal transplants such as adrenal chromaffin cells have been tried but do not survive although some L-dopa-producing cell lines (e.g. PC 12) or glomus cells of the carotid body do produce DA in vivo and may provide the equivalent of a continuous infusion of dopa (and DA) directly into the brain. Expression of tyrosine hydroxylase to promote dopa and DA synthesis in striatal cells by direct gene transfer in vivo or in cultures for subsequent transplanting, may also be possible. (See Dunnett and Bjorklund 1999 for a review of these approaches.)... 

Pheochromocytoma A tumor arising from chromaffin cells, most commonly found in the adrenal medulla. The tumor causes the adrenal medulla to hypersecrete epinephrine and norepinephrine, resulting in hypertension and other signs and symptoms of excessive sympathetic nervous system activity. The tumor is usually benign but may occasionally be cancerous. 

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... 

At least two classes of regulated secretion can be defined [54]. The standard regulated secretion pathway is common to all secretory cells (i.e. adrenal chromaffin cells, pancreatic beta cells, etc.) and works on a time scale of minutes or even longer in terms of both secretory response to a stimulus and reuptake of membranes after secretion. The second, much faster, neuron-specific form of regulated secretion is release of neurotransmitters at the synapse. Release of neurotransmitters may occur within fractions of a second after a stimulus and reuptake is on the order of seconds. Indeed, synaptic vesicles may be recycled and ready for another round of neurotransmitter release within 1-2 minutes [64]. These two classes of regulated secretion will be discussed separately after a consideration of secretory vesicle biogenesis. 

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... 

Neher, E. and Marty, A. Discrete changes of cell membrane capacitance observed under conditions of enhanced secretion in bovine adrenal chromaffin cells. Proc. Natl Acad. Sci. U.S.A. 79 6712-6716,1982. 

P2Y receptors that are found on endothelial cells elicit a Ca2+-dependent release of endothelium-dependent relaxing factor (EDRF) and vasodilation. A secondary activation of a Ca2+-sensitive phospholipase A2 increases the synthesis of endothelial prostacyclin, which limits the extent of intravascular platelet aggregation following vascular damage and platelet stimulation. The P2Y-mediated vasodilation opposes a vasoconstriction evoked by P2X receptors located on vascular smooth muscle cells. The latter elicit an endothelial-independent excitation (i.e. constriction). P2Y receptors are also found on adrenal chromaffin cells and platelets, where they modulate catecholamine release and aggregation respectively. 

To date, cellular and gene therapy products submitted to FDA have included clinical studies indicated for bone marrow marking, cancer, cystic fibrosis, AIDS, and inborn errors of metabolism and infectious diseases. Of the current active INDs approximately 78% have been sponsored by individual investigators or academic institutions and 22% have also been industry sponsored. In addition to the variety of clinical indications the cell types have also been varied. Examples include tumor infiltrating lymphocytes (TIL) and lymphocyte activated killer (LAK) cells, selected cells from bone marrow and peripheral blood lymphocytes, for example, stem cells, myoblasts, tumor cells and encapsulated cells (e.g., islet cells and adrenal chromaffin cells). 

Rauwolfia derivatives became available in the 1950s in western medicine for the treatment of hypertension. The antihypertensive effects of rauwolfia alkaloids occur from their depletion of monoamines in adrenal chromaffin cells and sympathetic ganglia, and perhaps central neurons as well (Oates 1996). 

Morita K, Hamano S, Oka M, Teraoka K. (1990). Stimulatory actions of bioflavonoids on tyrosine uptake into cultured bovine adrenal chromaffin cells. Biochem Biophys Res Commun. 171(3) 1199-204. 

Suh HW, Hudson PM, McMilhan MK, Das KP, Wilson BC, Wu GC, Hong JS (1995) Longterm stimulation of nicotinic receptors is required to increase proenkephahn AmRNA levels and the delayed secretion of [Met5]-enkephalin in bovine adrenal medullary chromaffin cells. J Pharmacol Exp Ther 275 1663-1670... 

Phaeochromocytoma (a tumor in the adrenal medulla) is not uncommon in rats, but rare in humans. Pheochromocytomas are induced in rats by a variety of non-genotoxic substances that may act indirectly by stimulating chromaffin cell proliferation. They are not known to be similarly inducible in other species. In the rat, a mechanism for the development may be hypercalcaemia (Tischler et al. 1999 Capen et ah, in Haschek et al. 2001). 

Catecholamines, such as epinephrine secreted by the chromaffin cells of the adrenal medulla or norepinephrine produced by the pancreas, have similar actions on metabolism to those of glucagon. 

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... 

The cells of the adrenal medulla, called chromaffin cells, are homologous with sympathetic postganglionic neurons. The adrenal medulla may in fact be considered a modified sympathetic ganglion. The adrenal medulla secretes two hormones. One is norepinephrine, which is also the primary neurotransmitter of sympathetic postganglionic neurons. The other medullary hormone is epinephrine. 

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