About Acetylcholine

Acetylcholine (ACh) is an organic chemical that functions in the brain and body of many types of animals, including humans, as a neurotransmitter—a chemical released by nerve cells to send signals to other cells.[1] Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Parts in the body that use or are affected by acetylcholine are referred to as cholinergic. Substances that interfere with acetylcholine activity are called anticholinergics.

Acetylcholine is the neurotransmitter used at the neuromuscular junction—in other words, it is the chemical that motor neurons of the Nervous system release in order to activate muscles. This property means that drugs that affect cholinergic systems can have very dangerous effects ranging from paralysis to convulsions. Acetylcholine is also used as a neurotransmitter in the autonomic nervous system, both as an internal transmitter for the sympathetic nervous system and as the final product released by the parasympathetic nervous system.

In the brain, acetylcholine functions as a neurotransmitter and as a neuromodulator. The brain contains a number of cholinergic areas, each with distinct functions. They play an important role in arousal, attention, memory and motivation.

Partly because of its muscle-activating function, but also because of its functions in the autonomic nervous system and brain, a large number of important drugs exert their effects by altering cholinergic transmission. Numerous venoms and toxins produced by plants, animals, and bacteria, as well as chemical nerve agents such as Sarin, cause harm by inactivating or hyperactivating muscles via their influences on the neuromuscular junction.

Drugs that act on muscarinic acetylcholine receptors, such as atropine, can be poisonous in large quantities, but in smaller doses they are commonly used to treat certain heart conditions and eye problems. Scopolamine, which acts mainly on muscarinic receptors in the brain, can cause delirium and amnesia. The addictive qualities of nicotine are derived from its effects on nicotinic acetylcholine receptors in the brain.

Acetylcholine (frequently abbreviated ACh) is the most widely spread neurotransmitter – chemical messenger assisting in carrying signals across the nerve synapse. It is the most plentiful neurotransmitter, which may be found in both the peripheral and central nervous systems (VandenBos, 2007). Acetylcholine used to be the primary neurotransmitter to be discovered. This neurotransmitter was found by Henry Hallett Dale in the year 1914 and its existence was confirmed by Otto Loewi (VandenBos, 2007).

It is helpful to think of neurotransmitters as messengers of the brain. These chemicals, which originate within the body, assist in delivering messages from one neuron to another. Basically, neurons that use acetylcholine to send the messages are recognized as cholinergic neurons. The pathway for their communication is the synapse. Neurotransmitters shift between synapses and join the receptors specially created to get messages only from that particular chemical (Whittaker, 1990). Upon this blending, nerve cells related to the receptor site are activated in one of two ways. Either they will fire in the excitatory reaction, or they will be averted from doing so in the inhibitory reaction.

FUNCTIONS OF ACETYLCHOLINE

• Acetylcholine performs as a transmitter at all neuromuscular (nerve-to-skeletal muscle) connections. It stimulates muscle contractions and, thus, all behavior.
• Acetylcholine is the transmitter of parasympathetic half of the autonomic nervous system.
• Acetylcholine is a transmitter in various brain regions (for instance, basal ganglia, cortex, and hypothalamus) and is required for proper memory and cognition, as well as motor control. The action of acetylcholine released at a synapse is ended through breakdown of ACh by enzyme acetylcholinesterase.

In particular, acetylcholine enhances the encoding of memories in the perirhinal and entorhinal cortex (Whittaker, 1990). Also, it prompts synaptogenesis, the normal development of synapses all through the brain (Whittaker, 1990). This additionally improves memory encoding, and helps other neurotransmitters to communicate messages (Colman, 2006). The lack of the necessary neuroplasticity may be the major aspect of diseases, such as ADHD and Alzheimer’s Disease.

Acetylcholine influences a large part of body systems counting the cardiovascular system by playing a role of a vasodilator, by lessening cardiac rate, and by lessening cardiac contraction; the gastrointestinal system by means of augmenting peristalsis in the stomach and by rising the number of digestive contractions; and, ultimately, the urinary tract by lessening the aptitude of the bladder and increasing the voiding pressure (VandenBos, 2007). Furthermore, acetylcholine influences the respiratory system and facilitates secretion by all glands, which respond to parasympathetic nerve impulses (VandenBos, 2007).

Importance of acetylcholine for the central nervous system: in the central nervous system, acetylcholine may be discovered mainly in interneurons. In this system, acetylcholine has numerous effects counting arousal and reward, as well as learning and short-term memory (via synaptic plasticity, the capability to alter the neuron connection strength).

A few significant long-axon cholinoceptive pathways have also been discovered. Remarkable is the cholinoceptive projection from the nucleus basalis of Meynert to the forebrain neocortex and linked limbic structures (Waymire, n.d.). Degeneration of the pathway is one of the medical conditions blamed on Alzheimer’s disease. There is also a projection from diagonal band region to limbic structures (Waymire, n.d.). The majority of subcortical areas are innerved by neurons from ponto-mesencephalic area.

Importance of acetylcholine for the peripheral nervous system: in the peripheral nervous system, acetylecholine plays a role of the neurotransmitter at the neuromuscular connection between skeletal muscle and motor nerve. It acts to effectively stimulate the muscle movement (Waymire, n.d.). ACh receptors on the muscles accept acetylcholine and lead to skeletal muscles’ contraction (Waymire, n.d.). It should also be mentioned that they make the heart muscles relax.

Importance of acetylcholine for the autonomic nervous system: in this case acetylcholine acts as the neurotransmitter in the preganglionic parasympathetic and sympathetic neurons. Acetylcholine also acts as the neurotransmitter at all the parasympathetic innerved organs, as well as at the sweat glands and at piloerector muscle of the sympathetic nervous system (Waymire, n.d.). As a neuromodulator, acetylcholine exists in the cerebrospinal fluid and control neurons directly rather than control via a single synaptic link (Waymire, n.d.).

NOOTROPICS THAT FURTHER BENEFIT ACETYLCHOLINE

Stimulating or increasing the level of Acetylcholine within the brain is possible through the use of a variety of nootropics.  Cholinergics work by further increasing the overall level of acetylcholine found present within the brain. CDP Choline, Alpha-GPC and Centrophenoxine are all examples of cholinergic nootropics. Several nootropics, such as most of the Racetam chemical class, work by stimulating the acetylcholine receptors found within the brain. Both of these benefits are further solidified through the “stacking” or combining of both cholinergic nootropics and nootropics that stimulate acetylcholine receptors.

Localized lesions and antagonist infusions demonstrate the anatomical locus of these cholinergic effects, and computational modeling links the function of cholinergic modulation to specific cellular effects within these regions. Acetylcholine has been shown to increase the strength of afferent input relative to feedback, to contribute to theta rhythm oscillations, activate intrinsic mechanisms for persistent spiking, and increase the modification of synapses. These effects might enhance different types of encoding in different cortical structures.

In particular, the effects in entorhinal and perirhinal cortex and hippocampus might be important for encoding new episodic memories. The role of ACh in attention has been repeatedly demonstrated in several tasks. Acetylcholine is linked to response accuracy in voluntary and reflexive attention and also to response speed in reflexive attention. It is well known that those with Attention-deficit/hyperactivity disorders tend to be inaccurate and slow to respond.

Within the autonomic nervous system, acetylcholine behaves in a similar manner, being discharged from the terminal of one neuron and binding to receptors on the postsynaptic membrane of other cells. Its activities within the autonomic nervous system affect a number of body systems, including the cardiovascular system, where it acts as a vasodilator, decreases heart rate, and decreases heart muscle contraction. In the gastrointestinal system, it acts to increase peristalsis in the stomach and the amplitude of digestive contractions. In the urinary tract, its activity decreases the capacity of the bladder and increases voluntary voiding pressure.

It also affects the respiratory system and stimulates secretion by all glands that receive parasympathetic nerve impulses. In the central nervous system, acetylcholine appears to have multiple roles. It is known to play an important role in memory and learning and is in abnormally short supply in the brains of persons with Alzheimer disease.

Acetylcholine is rapidly destroyed by the enzyme acetylcholinesterase and thus is effective only briefly. Inhibitors of the enzyme (drugs known as anticholinesterases) prolong the lifetime of acetylcholine. Such agents include physostigmine and neostigmine, which are used to help augment muscle contraction in certain gastrointestinal conditions and in myasthenia gravis. Other acetylcholinesterases have been used in the treatment of Alzheimer disease.

Naturally occurring acetylcholine was first isolated in 1913 by English chemist Arthur James Ewins, at the urging of his colleague, physiologist Sir Henry Dale, who in 1914 described the chemical’s actions. The functional significance of acetylcholine was first established about 1921 by German physiologist Otto Loewi. Loewi demonstrated that acetylcholine is liberated when the vagus nerve is stimulated, causing slowing of the heartbeat. Subsequently he and others showed that the chemical is also liberated as a transmitter at the motor end plate of striated (voluntary) muscles of vertebrates. It subsequently was identified as a transmitter at many neural synapses and in many invertebrate systems as well. Owing to Dale’s and Loewi’s work, acetylcholine became the first neurotransmitter to be identified and characterized. For their work, the two men shared the 1936 Nobel Prize for Physiology or Medicine.

Functions of Acetylcholine

Like mailpersons who can both deliver and pick up envelopes and packages, acetylcholine functions in the peripheral nervous system and central nervous system both as an activator and inhibitor. In the peripheral nervous system, it causes skeletal muscles to contract. In the central nervous system, it inhibits the activation of the cholinergic system.

Acetylcholine plays an important role in the signal of muscle movement, sensation of pain, learning and memory formation, the regulation of the endocrine system and rapid eye movement (REM) sleep cycles.

How to Change Your Levels of Acetylcholine

Increasing Acetylcholine

In order to increase your body’s levels of acetylcholine, you should increase choline levels. Choline can be found in a variety of sources [R].

When it comes to the herbs listed, they increase acetylcholine by inhibiting the enzyme that breaks them down – acetylcholinesterase.  Most common herbs have some inhibitory activity against the enzyme.

• Foods with Choline (Eggs, Liver)
• Choline supplements
• Bacopa (R)
• Huperzine A
• Epimedium (R),
• Caffeine (R),
• Blueberries (R),
• Zinc (R),
• Copper (R),
• Grape seed Extract (R),
• Rosemary,
• Cinnamon (R),
• Tulsi (R),
• Gotu Kola (R),
• Weaker:
• EGCG [R].
• Curcumin [R].
• Manganese, in the presences of citrate, increases acetylcholine synthesis [R].
• DHA and dietary fish oils [R].
• Luteolin enhances choline, which in turn increases acetylcholine in the body [R].
• Quercetin (high dose) (R),
• Fo-ti (R),
• Ashwagandha,
• Saffron (R)
• Reishi (R),
• Carvacrol (R),
• Rhodiola (R),
• Rehmannia (R)/Catalpol (R)
• Noni (R),
• Ginkgo,
• Peppermint,
• Schisandra (R),
• Magnesium (potentiates) (R),
• Andrographis (weak) (R),
• Fenugreek (R),
• Melatonin (R),
• Ginger (R),
• Danshen (R),
• Licorice (R),
• Sulforaphane (R),
• Ginseng (R),
• Propolis (R),
• Muira (R),
• Insulin (R),
• Fasting (R),
• Decreasing Acetylcholine
• A lot of drugs can inhibit acetylcholine, either by imitating it or inhibiting choline [R].
• Nicotine
• Forskolin,
• Kava,
• Lipoic Acid (in certain situations)
• Piracetam,
• Glycine in certain situations (R),
• Curare
• Mercury compounds
• Botulin

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