Synaptic actions

Obviously different NTs have different synaptic actions and it is of interest to see to what extent there are morphological correlates for these differing activities. 

Parkinsonism is unique among diseases of the CNS, in that it results from the known loss of a particular NT, i.e. DA, resulting from the degeneration of a particular pathway, the nigrostriatal. Dopamine also has a relatively limited distribution in the brain and few peripheral effects. It should therefore be amenable to therapy based on augmenting its function. Also since the role of DA appears to be to maintain a tonic inhibitory control on GABA output pathways from the striatum, possibly in part by an extra synaptic action (Chapter 6), it may not be necessary for it to be released physiologically from nerve terminals. Thus it may be adequate to just provide DA extracellularly. 

The synaptic action of acetylcholine is unique among neurotransmitters in that it is terminated by hydrolysis rather than by transport (Ch. 11). Consequently, cholinergic neurons recover choline, rather than acetylcholine, via... 

Autonomic erabutoxins polypept./post-synaptic action in blocking marine Laticauda... 

Dickinson R Selective synaptic actions of thiopental and its enantiomers. Anesthesiology 2002 96 884. [PMID 11964596]... 

The enzymes most important in the neurotransmission process are those that make and destroy the neurotransmitters. Thus, precursors are transported into the neuron with the aid of an enzyme-assisted transport pump and converted into neurotransmitters by a series of neurotransmitter-synthesizing enzymes (Figs. 1—7 through 1— 9). Once synthesis of the neurotransmitter is complete, it is stored in vesicles, where it stays until released by a nerve impulse. In the vesicle, the neurotransmitter is also protected from enzymes capable of breaking it down. Once released, however, the neurotransmitter is free not only to diffuse to its receptors for synaptic actions but also to diffuse to enzymes capable of destroying the neurotransmitter or to the reuptake pump already discussed above and represented in Figures 2-20 through 2-24. 

Figure 13.8. Schematic of pre- and post-synaptic actions of domoic acid.

Sellin, L.C., Thesleff, S. (1981). Pre- and post-synaptic actions of botulinum toxin at the rat neuromuscular junction. J. Physiol. 317 487-95. 

Getchell TV, Shepherd GM. 1975. Synaptic actions on mitral and tufted cells elicited by olfactory nerve volleys in the rabbit. J Physiol 251 497-522. 

Eccles JC, Elinas R, Sasaki K (1966a) The excitatory synaptic action of climbing fibers on the Purkinje cells of the cerebellum. J. Physiol, 182, 268-296. 

Schafer, T., Scwab, M.E. and Thoenen, H. (1983) Increased formation of preganglionic synapses and axons due to a retrograde trans-synaptic action and NGF in rat sympathetic nervous system. 7. Neurosci. 3 1501-1510. 

In addition to synthesis of new transmitter, NE stores are also replenished by transport ofNE previously released to the extracellular fluid by the combined actions of a NE transporter (NET, or uptake 1) that terminates the synaptic actions of released NE and returns NE to the neuronal cytosol, and VMAT-2, the vesicular monoamine transporter, that refills the storage vesicles from the cytosolic pool ofNE ("see below). In the removal ofNE from the synaptic cleft, uptake by the NET is more important than extraneuronal uptake (ENT, uptake 2). The sympathetic nerves as a whole remove -87% of released NE via NET compared with 5% by extraneuronal ENT and 8% via diffusion to the circulation. By contrast, clearance of circulating catecholamines is primarily by nonneuronal mechanisms, with liver and kidney accounting for >60% of the clearance. Because VMAT-2 has a much higher affinity for NE than does the metabolic enzyme, monoamine oxidase, over 70% of recaptured NE is sequestered into storage vesicles. 

Jaffrey, S. R., Cohen, N. A., Rouault, T. A., Klausner, R. D., and Snyder, S. H. (1994). The iron-responsive element binding protein A novel target for synaptic actions of nitric oxide. Proc. Natl. Acad. Sci. U.S.A. 91, 12994-12998. 

The opioid peptides are widely distributed in the CNS at all levels of the neuraxis and are synthesized in the cell bodies. They activate several receptor subtypes and cause inhibition. No mechanism has been described for termination of the synaptic actions of endogenous peptides. The answer is (E). 

Tricyclic antidepressants The acute effect of tricyclic drugs is to inhibit the reuptake mechanisms (transporters) responsible for the termination of the synaptic actions of both NE and 5-HT in the brain. This results in potentiation of their neurotransmitter actions at postsynaptic receptors. 

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