Acetylcholine parasympathetic transmitter

The basis for the antihypertensive activity of the ganglionic blockers lies in their ability to block transmission through autonomic ganglia (Fig. 20.2C). This action, which results in a decrease in the number of impulses passing down the postganglionic sympathetic (and parasympathetic) nerves, decreases vascular tone, cardiac output, and blood pressure. These drugs prevent the interaction of acetylcholine (the transmitter of the preganglionic autonomic nerves) with the nicotinic receptors on postsynaptic neuronal membranes of both the sympathetic and parasympathetic nervous systems. 

Q5 The parasympathetic transmitter acetylcholine is stored in synaptic vesicles within the postganglionic nerve ending. When an action potential arrives at the parasympathetic nerve terminal, the nerve ending depolarizes and... 

That transmission of the nervous impulse across synapses was chemical occurred to T.R. Elliott while still an undergraduate at Cambridge. Published work suggested to him that sympathetic nerve impulses released minute amounts of an agent that diffused across the synapse and was taken up on the far side (Elliott, 1905). Experimental confirmation was slow to arrive. Henry Dale (1914) supposed that acetylcholine could be the parasympathetic transmitter and, because it could not be detected, he further assumed that an enzyme must be nearby to hydrolyse it. Not until 1921 was there a convincing experimental proof of chemical transmission across this synapse (Loewi, 1921), and in 1926 the first neurotransmitter was finally identified and found to be acetylcholine (Loewi and Navratil, 1926). Dale was shown to be right about acetylcholinesterase, too. 

Acetylcholine (Ach) is an ester of acetic acid and choline with the chemical formula CH3COOCH2CH2N+ (CH3)3. ACh functions as a chemical transmitter in both the peripheral nervous system (PNS) and central nervous system (CNS) in a wide range of organisms, humans included. Neurotransmitter involved in behavioral state control, postural tone, cognition and memory, and autonomous parasympathetic (and preganglionic sympathetic) nervous system. 

Acetylcholine-mediated parasympathetic activity leads to production of the non-adrenergic-non-cholinergic transmitter nitric oxide. By enhancing the activity of guanylate cyclase, nitric... 

Neurotransmission in autonomic ganglia is more complex than depolarization mediated by a single transmitter 190 Muscarinic receptors are widely distributed at postsynaptic parasympathetic effector sites 190 Stimulation of the motoneuron releases acetylcholine onto the muscle endplate and results in contraction of the muscle fiber 191 Competitive blocking agents cause muscle paralysis by preventing access of acetylcholine to its binding site on the receptor 191... 

Somatic nerves originate in the CNS and terminate at the neuromuscular junction where acetylcholine is the transmitter. Nerves of the autonomic system also use acetylcholine as the neurotransmitter at the end of the preganglionic fibres within the ganglia. With few exceptions, the postganglionic sympathetic fibres secrete noradrenaline (norepinephrine) whilst postganglionic parasympathetic fibres secrete acetylcholine. 

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. 

Acetylcholine (ACh) as a transmitter. ACh serves as mediator at terminals of all postganglionic parasympathetic fibers, in addition to fulfilling its transmitter role at ganglionic synapses within both the sympathetic and parasympathetic divisions and the motor end-plates on striated muscle. However, different types of receptors are present at these synaptic junctions ... 

Fig. 1. Schematic drawing of the cholinergic neurotransmission. In case of ganglionic and neuro-muscular synapses, the receptor is of the nicotinic, sodium channel-coupled type, in case of synapses at the parasympathetic target organs, the receptor is of the muscarinic, G-protein-coupled type. The predominant ehinination pathway of the transmitter acetylcholine...

In the adrenal medulla and the ganglia of parasympathetic and sympathetic nerves, the neurotransmission is mediated by acetylcholine. On the postsynaptic membranes the transmitter activates the neuronal-type of the nicotinic acetylcholine receptor. This receptor type is in fact a sodium channel, its activation leads to a sodium influx and a membrane depolarization. A pharmacological interference at the... 

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. 

Like in the parasympathetic and ganglionic neurotransmission, the eliminating enzyme acetylcholine esterase is present at the postsynaptical membrane where it very efficiently reduces the free concentration of the transmitter. 

C. a-Adrenoceptors mediate contraction of the radial muscle of the iris. The shortening of the radial muscle cells opens the pupil. Phentolamine blocks a-adrenoceptors, allowing parasympathetic nerves innervating the sphincter muscle to take over. This leads to a less opposed contraction of the sphincter muscle induced by transmitter acetylcholine and a constriction of the pupil or miosis. 

The chemical transmitters may be small molecules— notably acetylcholine, norepinephrine, epinephrine, serotonin, dopamine, or histamine. Acetylcholine and norpeinephrine are the dominant neurotransmitters in the parasympathetic and sympathetic nervous systems, respectively. Dopamine and serotonin are employed primarily in the central nervous system. Neurotransmitters may also be more complex peptides (small proteins) such as substance P, vasopressin, endorphins, and enkephalins. The latter agents are of particular importance to our considerations of opium since they represent the endogenous opiates—agents that exist within the body whose actions are mimicked by exogenous, or outside, agents such as morphine, heroin, codeine, and so on. These neurotransmitters serve to convey information between neurons across the synaptic cleft (the junction where two neurons meet) or at the neuroeffector junction (the site between neuron and an innervated organ such as muscle or secretory gland). 

Schematic diagram comparing some anatomic and neurotransmitter features of autonomic and somatic motor nerves. Only the primary transmitter substances are shown. Parasympathetic ganglia are not shown because most are in or near the wall of the organ innervated. Cholinergic nerves are shown in blue noradrenergic in red and dopaminergic in green. Note that some sympathetic postganglionic fibers release acetylcholine or dopamine rather than norepinephrine. The adrenal medulla, a modified sympathetic ganglion, receives sympathetic preganglionic fibers and releases epinephrine and norepinephrine into the blood. ACh, acetylcholine D, dopamine Epi, epinephrine M, muscarinic receptors N, nicotinic receptors NE, norepinephrine.

A highly simplified diagram of the intestinal wall and some of the circuitry of the enteric nervous system (ENS). The ENS receives input from both the sympathetic and the parasympathetic systems and sends afferent impulses to sympathetic ganglia and to the central nervous system. Many transmitter or neuromodulator substances have been identified in the ENS see Table 6-1. ACh, acetylcholine AC, absorptive cell CM, circular muscle layer EC, enterochromaffin cell EN, excitatory neuron EPAN, extrinsic primary afferent neuron 5HT, serotonin IN, inhibitory neuron IPAN, intrinsic primary afferent neuron LM, longitudinal muscle layer MP, myenteric plexus NE, norepinephrine NP, neuropeptides SC, secretory cell SMP, submucosal plexus. 

Acetylcholine (ACh) The primary transmitter at ANS ganglia, at the somatic neuromuscular junction, and at parasympathetic postganglionic nerve endings. A primary excitatory transmitter to smooth muscle and secretory cells in the ENS. Probably also the major neuron-to-neuron ("ganglionic") transmitter in the ENS. 

Studies of neuromuscular junctions of the autonomic nervous system as early as 1904 led to the suggestion that adrenaline might be released at the nerve endings. Later it was shown that, while adrenaline does serve as a transmitter at neuromuscular junctions in amphibians, it is primarily a hormone in mammals. Nevertheless, it was through this proposal that the concept of chemical communication in synapses was formulated. By 1921, it was shown that acetylcholine is released at nerve endings of the parasympathetic system, and it later became clear the motor nerve endings of the somatic system also release acetylcholine. 

As indicated in Figure 18-1, the transmitter at the preganglionic-postganglionic synapse in both divisions is acetylcholine, as is the transmitter at the parasympathetic postganglionic-effector cell synapse. The transmitter at the sympathetic postganglionic-effector cell synapse is usually norepinephrine. A small number of sympathetic postganglionic fibers, however, also use acetylcholine as their neurotransmitter. 

Q4 The ganglionic transmitter of both divisions of the autonomic nervous system is acetylcholine. The major postganglionic neurotransmitter of the sympathetic nervous system is norepinephrine (noradrenaline), but a small number of structures are innervated by sympathetic, cholinergic fibres. These fibres release acetylcholine and the structures innervated include the sweat glands and blood vessels supplying skeletal muscle. In the parasympathetic system the postganglionic neurotransmitter is acetylcholine. 

Q6 In comparison with the sympathetic transmitter norepinephrine, the inactivation of acetylcholine by cholinesterases is rapid so that normally the activity of acetylcholine at the synapse is relatively short-lived. The choline component is taken up into the presynaptic terminal and acetylcholine is resynthesized and stored in the synaptic vesicles. Anticholinesterases function as cholinergic stimulants in the parasympathetic nervous system since they greatly prolong and so increase the actions of endogenous acetylcholine at muscarinic receptors on the effector tissue. 

Choline is an essential component of phospholipids - phosphatidylcholine (lecithin) is the major phospholipid in cell membranes and sphingomyelin is important in the nervous system. Acetylcholine is a transmitter in the central and parasympathetic nervous systems and at neuromuscular junctions, and has a role in the regulation of differentiation and development of the nervous system (Biagioni et al., 2000). Acetylcholine is also synthesized in mononuclear lymphocytes, where it has an autocrine or paracrine role in regulating immune function (Fujii and Kawashima, 2001). 

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