Cholinergic nerve terminal

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. 

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. 

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. 

Acetycholine is synthesised from choline and acetylcoenzyme A in the cholinergic nerve terminals. 

Beta Postsynaptic effector cells, especially heart, lipocytes, brain presynaptic adrenergic and cholinergic nerve terminals, juxtaglomerular apparatus of renal tubules, ciliary body epithelium Stimulation of adenylyl cyclase, increased cAMP... 

Transmitter synthesis Hemicholinium Cholinergic nerve terminals membrane Blocks uptake of choline and slows synthesis... 

Adrenergic and cholinergic nerve terminals Inhibition of transmitter release... 

Acetylcholine is destroyed too quickly and completely by AChE to be available for transport back into the presynaptic neuron, but the choline that is formed by its breakdown can be transported back into the presynaptic cholinergic nerve terminal by a transporter similar to the transporters for other neurotransmitters discussed earlier in relation to norepinephrine, dopamine, and serotonin neurons. Once back in the presynaptic nerve terminal, this choline can be recycled into acetylcholine synthesis (Fig. 12—8). 

In the mouse, whereas no evidence of H3 receptors was found in isolated gastric glands (Muller et al., 1993), in the whole stomach, (R)a-methylhistamine actually increased, and thioperamide decreased acid secretion, thus indicating a definite stimulatory role for H3 receptors in this species (Table 2). Apparently, this excitatory effect, which contrasts with the observations obtained in other models, was due to an inhibitory effect on somatostatin release from fundic D cells (Schubert et al., 1993 Vuyyuru and Schubert 1993). Also, an inhibitory effect on somatostatin secretion mediated by H3 agonists was observed in other species (rat and dog). However, contrarily to what might have been expected, in these species, the inhibitory effect on somatostatin is not followed by an increase in acid secretion, but it is instead followed by a decrease, owing to the predominant H3-mediated inhibition on the release of excitatory mediators (histamine, acetylcholine) from other sites (ECL, cholinergic nerve terminals)... 

Botulism was described much later than tetanus (Kemer 1817 Midura and Amon 1976 Pickett et al. 1976), and this delayed recognition is due to its much less evident symptoms, which include a generalized muscular weakness with diplopia, ptosis, dysphagia, facial paralysis, and reduced salivation and lacrimation. The paralysis then progressively descends to affect the muscles of the trunk, including respiratory and visceral muscles. All the symptoms of botulism can be ascribed to the blockade of skeletal and autonomic peripheral cholinergic nerve terminals (Tacket and Rogawski 1989). 

Muramatsu M, Tamaki-Ohashi J, Usuki C, Araki H, Aihara H (1988b) Serotonin-2 receptor-mediated regulation of release of acetylcholine by minaprine in cholinergic nerve terminal of hippocampus of rat. Neuropharmacology 27 603-9 Muramatsu M, Lapiz MD, Tanaka E, Grenhoff J (1998) Serotonin inhibits synaptic glutamate currents in rat nucleus accumbens neurons via presynaptic 5-HTjb receptors. Eur J Neurosci 10 2371-9... 

The effects of curare develop rapidly after it enters the body. Victims develop rapid weakness of voluntary muscles followed by paralysis, respiratory failure, and death. The cause is a blockade of nicotinic cholinergic receptors at the neuromuscular junctions in skeletal muscle. Unlike botulinum toxin, release of acetylcholine by the cholinergic nerve terminals is not affected. When curare is present, however, the acetylcholine that is released cannot bind to the receptors because they are reversibly occupied by the curare. As a consequence, nerve-muscle communication fails and paralysis ensues. 

The toxins that inhibit the AChE are called anticholinesterase (anti-ChE) agents. They cause acetylcholine to accumulate in the vicinity of cholinergic nerve terminals, and thus are potentially capable of producing effects equivalent to excessive stimulation of cholinergic receptors throughout the central and peripheral nervous systems (Long, 1963). Nevertheless, several members of this class of compounds are widely used as therapeutics agents others that cross the blood-brain barrier have been approved or are in clinical trial for the treatment of Alzheimer s disease. 

In general, sensitivity of a given preparation to clostridial neurotoxins depends on the type of neurotoxin. For instance, BoNT/A is particularly potent in poisoning peripheral cholinergic nerve terminals (i.e. neuromuscular junctions), whereas TeTx is most potent for CNS preparations. However, all eight neurotoxins are able to inhibit exocy-... 

Acetylcholinesterase (AChE) (also termed true cholinesterase ) is found in the synaptic cleft of cholinergic synapses, and is of undoubted importance in regulation of neurotransmission by rapid hydrolysis of released endogenous acetylcholine (ACh). AChE is also found in erythrocytes and in the CSF, and can be present in soluble form in cholinergic nerve terminals, but its function at these sites is not clear, AChE is specific for substrates that include acetylcholine and the agents methacholine and acetylthiocholine. but it has little activity with other esters. It has a maximum turnover rate at very low concentrations of AChE (and is inhibited by high concentrations). 

---