Other Autonomic Neurotransmitters

It is still uncertain whether all of these nonadrenergic, noncholinergic substances are true neurotransmitters. They may act as cotransmitters that are 

FIGURE 18-1 Autonomic neurotransmitters and receptors. Preganglionic neurons (solid lines] release acetylcholine [ACh], Postganglionic neurons [dashed lines] release ACh in the parasympathetic pathways and norepinephrine [NE] in the sympathetic pathways. 

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Regarding the NE system, loss of neurons in the LC and the existence of Lewy bodies have been shown by analysis of post mortem brains of PD patients (Zarow et ah, 2003) (Hoogendijk et ah, 1995) (Jellinger, 1991) (Chan-Palay and Asan, 1989). Reduced levels of NE in addition to disturbances in other related neurotransmitter system like the serotonergic may account for clinically relevant symptoms like depression, dementia, sleep disorders and autonomic dysfunction seen in PD. 

Figure 1. A depiction of the several different ionic currents necessary for the acute function of neuromuscular transmission in the skeletal motor and the efferent autonomic nervous system. The boxed current designations are associated, by the arrows, with those cellular regions where their physiological role is most evident, although these currents often exist in other regions of the cell. = neurotransmitter-activated current ...

The autonomic nervous system (ANS) modifies contractile activity of both types of smooth muscle. As discussed in Chapter 9, the ANS innervates the smooth muscle layer in a very diffuse manner, so neurotransmitter is released over a wide area of muscle. Typically, the effects of sympathetic and parasympathetic stimulation in a given tissue oppose each other one system enhances contractile activity while the other inhibits it. The specific effects (excitatory or inhibitory) that the two divisions of the ANS have on a given smooth muscle depend upon its location. 

The concept of chemical transmission in the nervous system arose in the early years of the century when it was discovered that the functioning of the autonomic nervous system was largely dependent on the secretion of acetylcholine and noradrenaline from the parasympathetic and sympathetic nerves respectively. The physiologist Sherrington proposed that nerve cells communicated with one another, and with any other type of adjacent cell, by liberating the neurotransmitter into the space, or synapse, in the immediate vicinity of the nerve ending. He believed that transmission across the synaptic cleft was unidirectional and, unlike conduction down the nerve fibre, was delayed by some milliseconds because of the time it took the transmitter to diffuse across the synapse and activate a specific neurotransmitter receptor on the cell membrane. 

More recently, a growing understanding of neurotransmitter modulation of appetitive behaviors has pointed to some disturbance of neurotransmitter function as the cause of AN and/or BN (Morley and Blundell, 1988 Fava et ah, 1989). It is possible that disturbances of brain neuropeptides and/or monoamines could contribute to other symptoms and behaviors, such as neuroendocrine or autonomic abnormalities, or alterations of mood and behavior in people with AN or BN. It is important to emphasize that monoamine or neuropeptide disturbances could be a consequence of dietary abnormalities, or premorbid traits that contribute to a vulnerability to develop AN or BN. One way to tease apart cause and effect is to study people with AN or BN at various stages in their illness—that is, while symptomatic and after recovery. 

Acetylcholine is a neurotransmitter, a key substance involved with transmission of nerve impulses in the brain, skeletal muscles, and other areas where nerve impulses occur. An essential step in the proper function of any nerve impulse is its cessation (see Figure 6.9), which requires hydrolysis of acetylcholine as shown by Reaction 6.10.1. Some xenobiotics, such as organophosphate compounds (see Chapter 18) and carbamates (see Chapter 15) inhibit acetylcholinesterase, with the result that acetylcholine accumulates and nerves are overstimulated. Adverse effects may occur in the central nervous system, in the autonomic nervous system, and at neuromuscular junctions. Convulsions, paralysis, and finally death may result. 

Norepinephrine Mostly excitatory, but inhibitory in some areas. Secreted by neurons in the locus ceruleus (subcortical area) to widespread areas of the brain, controlling wakefulness, overall activity, and mood. Also diffusely secreted in the sympathetic nervous system. Diffuse and widespread symptoms, including depression, changes in blood pressure, heart rate, and diffuse physiological responses, among many others. An important transmitter in the sympathetic branch of the autonomic nervous system. Diffusely affected by many medications. Several antidepressants work specifically on this neurotransmitter and its receptor sites. Many medications for general medical conditions affect this neurotransmitter as well. 

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