Cholinergic nerves

The neurotransmitter must be present in presynaptic nerve terminals and the precursors and enzymes necessary for its synthesis must be present in the neuron. For example, ACh is stored in vesicles specifically in cholinergic nerve terminals. It is synthesized from choline and acetyl-coenzyme A (acetyl-CoA) by the enzyme, choline acetyltransferase. Choline is taken up by a high affinity transporter specific to cholinergic nerve terminals. Choline uptake appears to be the rate-limiting step in ACh synthesis, and is regulated to keep pace with demands for the neurotransmitter. Dopamine [51 -61-6] (2) is synthesized from tyrosine by tyrosine hydroxylase, which converts tyrosine to L-dopa (3,4-dihydroxy-L-phenylalanine) (3), and dopa decarboxylase, which converts L-dopa to dopamine. 

Acetylcholine is synthesised in nerve terminals from its precursor choline, which is not formed in the CNS but transported there in free form in the blood. It is found in many foods such as egg yolk, liver and vegetables although it is also produced in the liver and its brain concentration rises after meals. Choline is taken up into the cytoplasm by a high-affinity (Am = 1-5 pM), saturable, uptake which is Na+ and ATP dependent and while it does not appear to occur during the depolarisation produced by high concentrations of potassium it is increased by neuronal activity and is specific to cholinergic nerves. A separate low-affinity uptake, or diffusion (Am = 50 pM), which is linearly related to choline concentration and not saturable, is of less interest since it is not specific to cholinergic neurons. 

Beta-bungarotoxin, a protein in cobra snake venom, also binds to cholinergic nerves to stop ACh release while a-bungarotoxin (from the same source) binds firmly to peripheral postsynaptic nicotinic receptors. The combined effect ensures the paralysis of the snake s victim. 

While there is no active neuronal uptake of ACh itself, cholinergic nerve terminals do possess autoreceptors. Since these are stimulated by ACh rather than by the choline, to which ACh is normally rapidly broken down, it is unlikely that they would be activated unless the synaptic release of ACh was so great that it had not been adequately hydrolysed by cholinesterase. 

Despite the paucity of nicotinic receptors in the brain there is considerable evidence that AzD is less common among smokers. Whether this is due to the action of inhaled nicotine is uncertain, but nicotine is known to stimulate presynaptic receptors on cholinergic nerve terminals which, unlike the muscarinic ones, result in increased ACh release. 

Dysfunction may be caused by aging, systemic inflammatory diseases, a decrease in androgen hormones, surgery, ocular surface diseases (such as herpes zoster), systemic diseases, or medications that affect the efferent cholinergic nerves. Decreased tear secretion produces an inflammatory response on the ocular surface called keratoconjunctivitis sicca. This inflammation is now a target for new medications that treat dry eye.29,30... 

Kristoikova Z and Klaschka J (1997). In vitro effect of Ginkgo biloba extract (EGb 761) on the activity of presynaptic cholinergic nerve terminals in rat hippocampus. Dementia <6 Geriatric Cognitive Disorders, 8, 43-48. 

The primary function of acetylcholinesterase is to terminate the activity of the neurotransmitter, acetylcholine (Fig. 6.4), through hydrolysis at the various cholinergic nerve endings. In this regard, it is probably the most highly efficient enzyme that operates in the human. It is capable of hydrolyzing 300,000 molecules of acetylcholine per molecule of enzyme... 

Furthermore, it has been demonstrated that ginsenoside Rbi increases the uptake of choline in central cholinergic nerve endings (Benishin, 1992), and facilitates the release of acetylcholine from hippocampal slices (Benishin et al, 1991 Lee et ah, 2001). These results clearly suggest that ginsenosides may facilitate learning and improve the basic synaptic transmission as well as nerve growth. 

Benishin, C. G. (1992). Actions of ginsenoside Rb on choline uptake in central cholinergic nerve endings. Neurochem. Int. 21,1-5. 

Hukovi CS, Stankovi CD, Brankov K. 1969. Effect of trinitrotoluene (TNT) and nitrobenzene on the effect of stimulation of cholinergic nerves of the bladder. Arh Hig Rada Toksikol 20 267-273. 

It has been repeatedly observed that atropine is more effective in blocking effects of exogenously introduced acetylcholine and other parasympathomimetics than in blocking effects resulting from stimulation of fibers of the parasympathetic and cholinergic nerves. There are two factors that could be the reason for this ... 

TABLE 9.1 Responses to Adrenergic and Cholinergic Nerve Stimulation... 

Transmission Step Adrenergic Nerves Cholinergic Nerves... 

Which of the following agents blocks the release of neurotransmitter from all cholinergic nerve endings ... 

Tacrine has been found to be somewhat effective in patients with mild-to-moderate symptoms of this disease for improvement of cognitive functions. The drug is primarily a reversible cholinesterase inhibitor that increases the concentration of functional ACh in the brain. However, the pharmacology of tacrine is complex the drug also acts as a muscarinic receptor modulator in that it has partial agonistic activity, as well as weak antagonistic activity on muscarinic receptors in the CNS. In addition, tacrine appears to enhance the release of ACh from cholinergic nerves, and it may alter the concentrations of other neurotransmitters such as dopamine and NE. 

Effect on eye Atropine produces mydriasis by blocking the cholinergic nerves supplying the smooth muscles of sphincter of the iris on local administration into the eye. It also produces paralysis of accommodation or cycloplegia (the condition in which, one can see things... 

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