Cholinergic neurotransmitters metabolism

The primary mechanism used by cholinergic synapses is enzymatic degradation. Acetylcholinesterase hydrolyzes acetylcholine to its components choline and acetate it is one of the fastest acting enzymes in the body and acetylcholine removal occurs in less than 1 msec. The most important mechanism for removal of norepinephrine from the neuroeffector junction is the reuptake of this neurotransmitter into the sympathetic neuron that released it. Norepinephrine may then be metabolized intraneuronally by monoamine oxidase (MAO). The circulating catecholamines — epinephrine and norepinephrine — are inactivated by catechol-O-methyltransferase (COMT) in the liver. 

Strong et al. 1996). Studies in these animals indicate that exposure to aluminum can affect permeability of the blood-brain barrier, cholinergic activity, signal transduction pathways, lipid peroxidation, and glucose metabolism, as well as interfere with metabolism of essential trace elements (e.g., iron) because of similar coordination chemistries and consequent competitive interactions. Signal pathways are important in all cells and control differentiation and proliferation, neurotransmitter release,... 

The alterations produced by THC and other cannabinoids in biogenic amine levels as well as on uptake, release and synthesis of neurotransmitters and effects on enzymes have been the subject of numerous investigations (for reviews see [8,52,55,114,115]). It is beyond the scope of the present summary to try to analyse and put into a proper perspective the wealth of data published so far. It is our subjective view that the mode of action of cannabi-mimetic compounds is somehow directly associated with prostaglandin metabolism (see, in particular, the series of papers by Burstein [115,116]), and/or reduction of hippocampal acetylcholine turnover observed in rats [117,118]. The latter effect is enantiospecific and follows the known SAR of the cannabinoids. This in vivo selectivity of action suggests that the THC may activate specific transmitter receptors which indirectly modulate the activity of the cholinergic neurons in the septalhippocampal pathway. 

In Chapter 8, peripheral aspects of the cholinergic system were considered. The basics of the neuron (Fig. 8-1), specifically the cholinergic neuron (Fig. 8-5), the synapse (Fig. 8-2), and depolarization (Fig. 8-3), were also presented. The significance and chemistry of acetylcholine (ACh) was discussed. Chapter 9 continued with the remainder of the peripheral autonomic nerve plan (i.e., the sympathetic, or adrenergic, system). The biosynthesis of the catecholamines DA, NE, and EP were discussed and illustrated (Fig. 9-1), and the metabolism schemes for NE and EP (Fig. 9-3) and DA (Fig. 9-4) were outlined. Much of the early (before 1960) neurochemistry elucidated, and neurotransmitters identified, were central to the functioning of the peripheral nervous system. 

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