Autonomic nervous system transmission

The locus cemleus is important for the regulation of attentional states and autonomic nervous system activity. It has also been implicated in the autonomic and stress-like effects of opiate withdrawal. A noradrenergic pathway originating from the locus cemleus which descends into the spinal cord is part of the descending inhibitory control system, which has an inhibitory effect on nociceptive transmission in the dorsal horn. 

Neurohumoral transmitters are chemicals that facilitate the transmission of nerve impulses across nerve synapses and neuroeffector junctions. Acetylcholine is a neurohumoral transmitter that is present in the peripheral autonomic nervous system, in the somatic motor nervous system, and in some portions of the central nervous system. 

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 concept of chemical neurotransmission originated in the 1920s with the classic experiments of Otto Loewi (which were themselves inspired by a dream), who demonstrated that by transferring the ventricular fluid of a stimulated frog heart onto an unstimulated frog heart he could reproduce the effects of a (parasympathetic) nerve stimulus on the unstimulated heart (Loewi Navratil, 1926). Subsequently, it was found that acetylcholine was the neurotransmitter released from these parasympathetic nerve fibers. As well as playing a critical role in synaptic transmission in the autonomic nervous system and at vertebrate neuromuscular junctions (Dale, 1935), acetylcholine plays a central role in the control of wakefulness and REM sleep. Some have even gone as far as to call acetylcholine a neurotransmitter correlate of consciousness (Perry et al., 1999). 

The answers arc 488-d, 489-h. (Katzang, pp 108-112, 1020.) Atropine blocks muscarinic cholinergic transmission in the brain and in the autonomic nervous system. The result is dry mouth, thirst, dry and hot skin, tachycardia, urinary retention, ataxia, restlessness, excitement, and hallucinations, followed by stupor, delirium, respiratory depression, coma, and death. 

ACh is necessary for control of skeletal muscle in verterbrates, acting as the neurotransmitter at the neuromuscular junction. It is also involved in transmission in the autonomic nervous system (see below, under "Neuroanatomy"). Central ACh is produced in two general areas in the brain incuding the basal forebrain (medial septal nuclei, diagonal band... 

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. 

Beside the efferent innervation by the autonomic nervous system there are peripheral afferent sensory fibers which form the autonomic refiex arcs. They play a major role in the transmission of visceral sensations and are responsible for visceral refiexes, for example in the autonomic regulation of the blood pressure. 

Atropine, an alkaloid from Atropa belladonna, is the classical parasympatholytic compound. It competes with acetylcholine for the binding at the muscarinic receptor. Its affinity towards nicotinic receptors is very low, so that it does not interfere with the ganglionic transmission or the neuromotor transmission, at least in therapeutic dosages. However, in the central nervous system muscarinic receptor do play an important role and while atropine can penetrate the blood-brain barrier it exerts pronounced central effects. Atropine, like all other antagonists of the muscarinic acetylcholine receptor inhibit the stimulatory influence of the parasympathetic branch of the autonomous nervous system. All excretory glands (tear, sweat, salivary, gasto-intestinal, bronchi) are... 

Beside this there are some major differences with the neurotransmission in the autonomous nervous system The contractile activity of the skeletal muscle is almost completely dependent on the innervation. There is no basal tone and a loss of the innervation is identical to a total loss in function of the particular skeletal muscle. In contrast to the target organs of the parasympathetic nervous system the skeletal muscle cells only have acetylcholine receptors at the site of the so-called end-plate, the connection between neuron and muscle cell with the rest of the cell surface being insensitive to the transmitter. The release of acetylcholine results in a postjunctional depolarization which is either above the threshold to induce an action potential and a contraction or below the threshold with no contractile response at all. In contrast to the graduated reactions of the parasympathetic target organs, this is an all or nothing transmission. 

The biology of the monoamines is described in detail elsewhere. In simple terms, they facilitate transmission in neural pathways that originate in nuclei of the brainstem and have descending projections to the autonomic nervous system and widespread ascending projections to sites in the limbic system and cortex. These pathways modulate many aspects of behavioural function as well as anxiety responses. Of the three monoamines, the role of serotonin in anxiety is best understood, but the picture is complex as increased serotonergic activity may be anxiogenic or anxiolytic depending on the site of action (Bell and Nutt 1998). 

Ang II also interacts with the autonomic nervous system. It stimulates autonomic ganglia, increases the release of epinephrine and norepinephrine from the adrenal medulla, and—what is most important—facilitates sympathetic transmission by an action at adrenergic nerve terminals. The latter effect involves both increased release and reduced reuptake of norepinephrine. Ang II also has a less important direct positive inotropic action on the heart. 

Acetylcholine is a neurotransmitter that functions in conveying nerve impulses across synaptic clefts within the central and autonomic nervous systems and at junctures of nerves and muscles. Following transmission of an impulse across the synapse by the release of acetylcholine, acetylcholinesterase is released into the synaptic cleft. This enzyme hydrolyzes acetylcholine to choline and acetate and transmission of the nerve impulse is terminated. The inhibition of acetylcholineasterase results in prolonged, uncoordinated nerve or muscle stimulation. Organophosphorus and carbamate pesticides (Chapter 5) along with some nerve gases (i.e., sarin) elicit toxicity via this mechanism. 

The appearance of mass movements after meals is caused at least partially by gastrocolic and duodenocolic reflexes. These reflexes result from distension of the stomach and duodenum. They can take place, although with decreased intensity, when the autonomic nerves are removed therefore, it is probable that the reflexes are basically transmitted through the myenteric plexus, although reflexes conducted through the autonomic nervous system probably reinforce this direct route of transmission. 

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. 

In many ways, the basic functioning of neurons in the CNS is similar to that of the autonomic nervous system described in Chapter 3. For example, transmission of information in the CNS and in the periphery both involve the release of neurotransmitters that diffuse across the synaptic space to bind to specific receptors on the postsynaptic neuron. In both systems, the recognition of the neurotransmitter by the membrane receptor of the postsynaptic neuron triggers intracellular changes (see p. 33). Several major differences exist between neurons in the peripheral autonomic nervous system and those of the CNS. The circuitry of the CNS is much more complex than the autonomic nervous... 

Adrenergic transmission is well known to be involved in the regulation of homeostatic control through its functions in the autonomic nervous system. Additionally, adrenergic projections in the brain have been identified with important roles in neurocognition. Adrenoreceptors are seven transmembrane G-protein-coupled receptors that mediate the physiological responses of epinephrine and norepinephrine. The first classification of these receptors resolved a (alpha)-adrenoreceptors (aARs) from P (beta)-adrenoreceptors (PARs) (Ahlquist, 1948). Since then, additional subtypes and variants have been described. 

It was only after the role of acetylcholine in the functioning of the autonomic nervous system, in neuroeffector transmission to the various entitles Innervated by that system and to skeletal muscles (3-11), and In synaptic transmission within some areas of the central and peripheral nervous systems (12-17) had been demonstrated that the proximate mechanism of action of atropine, scopolamine, and ocher compounds of similar activity could be understood, niese c[Pg.133]

Tobacco smoke includes 4000 chemical species with varying potential which cause adverse effects. Nicotine is stimulating to the autonomic nervous system ganglia and neuromuscular junction. The most prominent effects relate to stimulation of the adrenal medulla, central nervous system (CNS), cardiovascular system (release of catecholamines), gastrointestinal tract (parasympathetic stimulation), salivary and bronchial glands, and the medullary vomiting center. There is subsequent blockade of autonomic ganglia and the neuromuscular junction transmission, inhibition of catecholamine release from the adrenal medulla, and CNS depression. 

In the peripheral nervous system, norepinephrine is an important neurotransmitter in the sympathetic branch of the autonomic system. Sympathetic nerve transmission operates below the level of consciousness in controlling physiological function of many organs and tissues of the body. The sympathetic system plays a particularly important role in regulating cardiovascular function in response to postural, exertional, thermal, and mental stress. With sympathetic activation, the heart rate is increased, peripheral arterioles are constricted, skeletal arterioles are dilated, and the blood pressure is elevated. In addition, sympathetic nerve stimulation dilates pupils inhibits smooth muscles of the intestines, bronchi, and bladder and closes the sphincters. Sympathetic signals work in balance with the parasympathetic portion of the autonomic nervous system to maintain a stable internal environment. 

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