Peripheral nervous system products

The nervous system is a complex part of the human body concerned with die regulation and coordination of body activities such as movement, digestion of food, sleep, and elimination of waste products. The nervous system has two main divisions the central nervous system (CNS) and the peripheral nervous system (PNS). Figure 22-1 illustrates the divisions of die nervous system. 

NO is a gaseous neurotransmitter implicated in signaling in the central and peripheral nervous system as well as in the immune system and the vasculature. NO is formed from L-arginine by nitric oxide synthase (NOS). There are three isoforms of NOS. All isoforms require NADPH as a cofactor, use L-arginine as a substrate, and are inhibited by Nw-nitro-L-arginine methyl ester (L-NAME). The three isoforms are separate gene products. One isoform of NOS is a cytosolic, calcium/calmodulin-independent, inducible enzyme (iNOS). It is found in macrophages, neutrophils, vascular smooth muscle, and endothelia. The iNOS... 

Many cytokines play a regulatory role in processes other that immunity and inflammation. Neurotrophic factors, such as NGF and BDNF, regulate growth, development and maintenance of various neural populations in the central and peripheral nervous system. EPO stimulates the production of red blood cells from erythroid precursors in the bone marrow. 

The rate-limiting step in the synthesis of the catecholamines from tyrosine is tyrosine hydroxylase, so that any drug or substance which can reduce the activity of this enzyme, for example by reducing the concentration of the tetrahydropteridine cofactor, will reduce the rate of synthesis of the catecholamines. Under normal conditions tyrosine hydroxylase is maximally active, which implies that the rate of synthesis of the catecholamines is not in any way dependent on the dietary precursor tyrosine. Catecholamine synthesis may be reduced by end product inhibition. This is a process whereby catecholamine present in the synaptic cleft, for example as a result of excessive nerve stimulation, will reduce the affinity of the pteridine cofactor for tyrosine hydroxylase and thereby reduce synthesis of the transmitter. The experimental drug alpha-methyl-para-tyrosine inhibits the rate-limiting step by acting as a false substrate for the enzyme, the net result being a reduction in the catecholamine concentrations in both the central and peripheral nervous systems. 

Other actions of kinins include activation of clotting factors simultaneously with the production of bradykinin. In the kidney, bradykinin production results in an increase in renal papillary blood flow, with a secondary inhibition of sodium reabsorption in the distal tubule. In the peripheral nervous system, bradykinin is important for the initiation of pain signals. It is also associated with the edema, erythema, and fever of inflammation. 

For almost one century, acetylcholine has been recognized as a neurotransmitter both in the central nervous system and the peripheral nervous system. In the peripheral nervous system, acetylcholine has been identified as the neurotransmitter of autonomic ganglia and the neuromuscular junction. Acetylcholine is involved in different peripheral functions such as heart rate, blood flow, gastrointestinal tract motility, and sweat production and smooth muscle activity. In the CNS, cholinergic neurotransmission plays a crucial role in a variety of CNS functions including sensory perception, motor function, cognitive processing, memory, arousal, attention, sleep, nociception, motivation, reward, mood, and psychosis. 

Norepinephrine (NE), a catecholamine, was first identified as a neurotransmitter in 1946. In the peripheral nervous system, it is found as a neuro transmitter in the sympathetic postganglionic synapse. NE is synthesized by the enzyme dopamine-p-hydroxylase (DbH) from the precursor dopamine (which is derived from tyrosine via DOPA). The rate-limiting step is the production of DOPA by tyrosine hydroxylase, which can be activated through phosphorylation. NE is removed from the synapse by two mechanisms (1) catechol-O-methyl-transferase (COMT), which degrades intrasynaptic NE, and (2) the norepinephrine transporter (NET), the primary way of removing NE from the synapse. Once internalized, NE can be degraded by the intracellular enzyme monoamine oxidase (MAO). 

Leskovar A, Moriarty LJ, Turek JJ, Schoenlein lA, Borgens RB (2000) The macrophage in acute neural injury Changes in cell numbers over time and levels of cytokine production in mammalian central and peripheral nervous systems. J Exp Biol 203 1783-1795. 

DOPA to dopamine, by the cytosolic enzyme, DOPA decarboxylase. In the central and peripheral nervous systems, dopamine is converted to noradrenaline by dopamine-P-hydroxylase (DBH), which, though a relatively non-specific enzyme, is restricted to catecholamine-synthesizing cells. It can be inhibited by many drugs, which brings the risk of complex drug interactions. In the peripheral sympathetic nervous system, noradrenaline, in turn, is converted to adrenaline, by phenylethylamine N-methyl transferase, so inhibition of DBH can therefore, in principle, slow production of both adrenaline and noradrenaline but normally tyrosine hydroxylase is the rate-limiting step in the synthetic pathway. 

Exposures to xenobiotics affect OS adversely by increasing the body s ROS and thereby upsetting the balance between the natural production and elimination of free radicals. OS has been implicated in numerous deleterious conditions brought about by xenobiotic exposures in humans. These conditions include infertility, central and peripheral nervous system effects, respiratory effects, liver and kidney function, cardiovascular effects, and cancer. Each of these is addressed in the ensuing chapters. 

They found it to be a useful marker for CNS tissue and, more specifically, a useful marker for differentiating between CNS tissue and tissues of the peripheral nervous system in AMR products (Kelley et al., 2000). 

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