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Wednesday, July 11, 2012

Acetylcholine



Acetylcholine is a neurotransmitter that control several vital functions like breathing, heart rate and deliberate muscle control. Body has 2 basic types of acetylcholine receptors and both have seriously important roles.  
Nicotinic acetylcholine receptors (nicotine also activates it) are rare in nervous system but common on skeletal muscles that animals can move deliberately. If those are blocked humans can't move and even their lungs can become so paralyzed they could suffocate. Blocker of these receptors are sometimes used during surgeries to relax muscles and sometimes it causes wakings where people feel pain but can't move. Also these drugs paralyze breathing so machine has to pump air into and out of lungs.
Muscarinic acetylcholine receptors are also activated by muscarine from and if they are active they cause sweating, nausea, vomiting, active mucus membranes, more salivation, slowed heart rate, slowed breathing (vagal reflexes are mediated by muscarinic receptors) and in hippocampus they are needed to remember events. Fly agaric causes drowsy and sweaty state.
These receptors can be blocked with atropine and scolopamine. These substances cause hallucinations of talking to someone who isn't there and makes people see objects they see sometimes as real. These substances are called deliriants due to causing believable hallucinations. Erowid has many personal experiences where people took deliriants. As side effect deliriants also block sweating and heart rate may become lethally fast due to suppressed vagal nerve.

Even deliriants have been allowed for special cases like chemical weapon attacks. As they block excess acetylcholine activity then they can keep people alive through chemical weapon attack although people could get very confused and probably will not remember much. Muscarinic receptor blockers are also medically used to stimulate heart rate as it would reduce vagal nerve activity that keeps heart from working too hard.

One other important protein that can be abused is acetylcholinesterase that breaks up acetylcholine around cells. Many chemical weapons (VX, sarin) and insecticides (DEET) block this enzyme causing sometimes deadly muscle spasms and suffocation to anyone from insects to humans as these proteins seem to be present in all species i've checked.    

For example i randomly chose human muscarinic M3 receptor with fruit fly rceptors and closest match was 60% identity with fruit flies muscarinic receptors. Among other results human M3 was about 40% identical with fruit flies serotonin, octopamine (noradrenaline to invertebrates) and dopamine receptors.

When comparing human nicotinic receptor with fruit flies it had 58% identity with fruit flies nicotine receptor. Also several ion channels were among results as nicotinic receptor is also ion channel. Muscarinic receptors are regulators of cell metabolism.

Human acetylcholinesterase had 36% identity with same protein in fruit fly. Maybe this larger difference made acetylcholine blocker preferred insecticide.

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