Cholinergic neurons Subject

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. 

Compatible with previous findings (Perry et al, 2004 Perry and Soreq, 2004 Sklan et al, 2004), AChE-R appears to contribute to the maintenance of cholinergic homeostasis while accentuating neuronal inflammatory reactions. Because AChE-R accumulation reduces ACh levels, suppression of AChE-R overproduction can retrieve the blockade over pro-inflammatory cytokine production, suppressing the inflammatory status in treated subjects. 

TERMINATION OF THE ACTIONS OF CATECHOLAMINES The actions of NE and Epi are terminated by (1) reuptake into nerve terminals by NET (2) dilution by diffusion out of the junctional cleft and uptake at end organs and extraneuronal sites by ENT, OCTl, and OCT2. Subsequent to uptake, the catecholamines are subject to metabolic transformation by MAO and catechol-0-methyltransferase (COMT). In addition, catecholamines are metabolized by sulfotransferases (see Chapter 3). Termination of action by a powerful degradative enzymatic pathway, such as that provided by AChE in cholinergic transmission, is absent from the adrenergic system. Inhibitors of neuronal reuptake of catecholamines (e.g., cocaine, imipramine) potentiate the effects of the... 

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