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The parasympathetic nervous system, which uses acetylcholine almost exclusively to send its messages, is said to be almost entirely cholinergic. Neuromuscular junctions, preganglionic neurons of the sympathetic nervous system , the basal forebrain , and brain stem complexes are also cholinergic, as are the receptor for the merocrine sweat glands.
Acetylcholine (ACh) is an excitatory, small-molecule neurotransmitter involved in synaptic transmission at neuromuscular junctions controlling the vagus nerve and cardiac muscle fibers, as well as in the skeletal and visceral motor systems and various sites within the central nervous system. [3]
Acetylcholine is a choline molecule that has been acetylated at the oxygen atom. Because of the charged ammonium group, acetylcholine does not penetrate lipid membranes. . Because of this, when the molecule is introduced externally, it remains in the extracellular space and at present it is considered that the molecule does not pass through the blood–brain
Whittaker's work demonstrating acetylcholine in vesicle fractions from guinea-pig brain was first published in abstract form in 1960 and then in more detail in 1963 and 1964, [36] [37] and the paper of the de Robertis group demonstrating an enrichment of bound acetylcholine in synaptic vesicle fractions from rat brain appeared in 1963. [38]
This prevents interaction between the acetylcholine released by the presynaptic terminal and the receptors on the postsynaptic cell. In effect, the opening of sodium channels associated with these acetylcholine receptors is prohibited, resulting in a neuromuscular blockade, similar to the effects seen due to presynaptic neurotoxins.
Acetylcholine is known to promote wakefulness in the basal forebrain. Stimulating the basal forebrain gives rise to acetylcholine release, which induces wakefulness and REM sleep, whereas inhibition of acetylcholine release in the basal forebrain by adenosine causes slow wave sleep.
Choline acetyltransferase was first described by David Nachmansohn and A. L. Machado in 1943. [6] A German biochemist, Nachmansohn had been studying the process of nerve impulse conduction and utilization of energy-yielding chemical reactions in cells, expanding upon the works of Nobel laureates Otto Warburg and Otto Meyerhof on fermentation, glycolysis, and muscle contraction.
Similarly, acetylcholine released from parasympathetic neurons may interact with M 2 and M 4 receptors to inhibit further release of acetylcholine. An atypical example is given by the β-adrenergic autoreceptor in the sympathetic peripheral nervous system, which acts to increase transmitter release. [1]