Acetylcholine release

Several cholinergic strategies, other than cholinesterase inhibition, have been employed with the intention of ameliora ting the symptoms of AD. These include precursor loading acetylcholine release enhancement, and direct activation of both muscarinic and nicotinic receptors. 

Dronabinol (tetrahydrocannabinol), the active principle from cannabis and synthetic cannabinoids, nabilone and levonantradol are effective in treating nausea and vomiting in cancer chemotherapy. The mode of action is unclear but appears to involve cannabinoid CBi receptors. Cannabinoids have been shown to reduce acetylcholine release in the cortex and hippocampus, and have been suggested to inhibit medullary activity by a cortical action. Inhibition of prostaglandin synthesis and release of endorphins may also be involved in the antiemetic effect. A review of trials of dronabinol, nabilone or levonantradol concluded that while the cannabinoids were superior to placebo or dopamine receptor antagonists in controlling emesis... 

A related organism, CL botulinum, produces a similar toxin which may contaminate food if the organism has grown in it and conditions are favourable for anaerobic growth. Meat pastes and pates are likely sources. This toxin interferes with acetylcholine release at cholinergic syrrapses and also acts at neuromuscular jimctions. Death fiom this toxin eventually results firm respiratory failure. 

Figure 6.8 ACh release and cortical activity. Correlation between acetylcholine release and EEG activity after injections of leptazol (LEPmgkg intravenously) into the urethane anaesthetised rat. ACh was collected in a cortical cup incorporating EEG recording electrodes. Mean values SE, n — 6 (unpublished data, but see Gardner and Webster 1977)...

Gardner, CR and Webster, RA (1977) Convulsant-anticonvulsant interactions on seizure activity and cortical acetylcholine release. Eur. J. Pharmacol. 42 247-256. 

Leventer, S.M., and Johnson, K.M. Phencyclidine-induced inhibition of striatal acetylcholine release Comparisons with mu, kappa, and sigma opiate agonists. I i f e Sci 34 793-801, 1984. 

Cannabimimetics reduce the intestinal motility by a CB1-mediated inhibitory activity on acetylcholine release from autonomic fibers. An endo-cannabinoid, 2-AG, was isolated from dog intestine however, its role there remains unknown (Mechoulam, 1995a). 

Figure 9 Graph of inhibition of acetylcholine release in superfused hippocampal slices versus CB1 receptor occupancy estimated from inhibition of [131I]AM281 binding.

Gifford AN, Tang Y, Gatley SJ, Volkow ND, Lan R, Makriyannis A. Effect of the cannabinoid receptor SPECT agent, AM 281, on hippocampal acetylcholine release from rat brain slices. Neurosci Lett 1997 238 84-86. 

Gifford AN, Ashby CR. Electrically evoked acetylcholine release from hippocampal slices is inhibited by the cannabinoid receptor agonist, WIN 55212-2, and is potentiated by the cannabinoid antagonist, SR 141716A. J Pharmacol Exp Ther 1996 277 1431-1436. 

Figure 14.1 Effect of autonomic nervous system stimulation on action potentials of the sinoatrial (SA) node. A normal action potential generated by the SA node under resting conditions is represented by the solid line the positive chronotropic effect (increased heart rate) of norepinephrine released from sympathetic nerve fibers is illustrated by the short dashed line and the negative chronotropic effect (decreased heart rate) of acetylcholine released from parasympathetic nerve fibers is illustrated by the long dashed line.

Roth, M. T., Fleegal, M. A., Lydic, R. Baghdoyan, H. A. (1996). Pontine acetylcholine release is regulated by muscarinic autoreceptors. Neuroreport 7, 3069-72. 

Vazquez, J. Baghdoyan, H. A. (2004). GABAA receptors inhibit acetylcholine release in cat pontine reticular formation implications for REM sleep regulation. J. Neurophysiol. 92, 2198-206. 

Celesia, G. G. Jasper, H. H. (1966). Acetylcholine released from cerebral cortex in relation to state of activation. Neurology 16, 1053-64. 

Coleman, C. G., Baghdoyan, H. A. 8r Lydic, R. (2006). Dialysis delivery of an adenosine A2A agonist into the pontine reticular formation of C57BL/6J mouse increases pontine acetylcholine release and sleep. J. Neurochem. 96, 1750-9. 

Douglas, C. L., Baghdoyan, H. A. Lydic, R. (2002b). Prefrontal cortex acetylcholine release, EEG slow waves, and spindles are modulated by M2 autoreceptors in C57BL/6J mouse. J. Neurophysiol. 87, 2817-22. 

Kodama, T., Takahashi, Y. Honda, Y. (1990). Enhancement of acetylcholine release during paradoxical sleep in the dorsal tegmental field of the cat brain stem. Neurosci. Lett. 114, 277-82. 

Leonard, T. O. Lydic, R. (1995). Nitric oxide synthase inhibition decreases pontine acetylcholine release. Neuroreport 6, 1525-9. 

Leonard, T. 0. Lydic, R. (1997). Pontine nitric oxide modulates acetylcholine release, rapid eye movement sleep generation, and respiratory rate. J. Neurosci. 17, 774-85. 

Lydic, R., Baghdoyan, H. A. Lorinc, Z. (1991). Microdialysis of cat pons reveals enhanced acetylcholine release during state-dependent respiratory depression. Am. J. Physiol. 261, R766-70. 

Lydic, R., Keifer, J. C., Baghdoyan, H. A. Becker, L. (1993). Microdialysis of the pontine reticular formation reveals inhibition of acetylcholine release by morphine. Anesthesiology 79, 1003-12. 

---