Neurotransmitters release

Stimulation of the neuron lea ding to electrical activation of the nerve terminal in a physiologically relevant manner should eUcit a calcium-dependent release of the neurotransmitter. Although release is dependent on extracellular calcium, intracellular calcium homeostasis may also modulate the process. Neurotransmitter release that is independent of extracellular calcium is usually artifactual, or in some cases may represent release from a non-neuronal sources such as gha (3). 

Numerous processes modulate neurotransmitter synthesis, presynaptic excitabihty, neurotransmitter release, post-synaptic receptors, and post-synaptic excitabihty. 

Long-lasting vasoconstriction is produced by the ETs in almost all arteries and veins and several studies have shown that ET-1 causes a reduction in renal blood flow and urinary sodium excretion. ET-1 has been reported to be a potent mitogen in fibroblasts and aortic smooth muscle cells and to cause contraction of rat stomach strips, rat colon and guinea pig ileum. In the central nervous system, ETs have been shown to modulate neurotransmitter release. 

Dmgs that mimic or inhibit the actions of neurotransmitters released from parasympathetic or sympathetic nerves innervating the heart may also be used to treat supraventricular bradyarrhythmias, heart block, and supraventricular tachyarrhythmias. Those used in the treatment of arrhythmias may be found in Table 1. 

Adenosine is produced by many tissues, mainly as a byproduct of ATP breakdown. It is released from neurons, glia and other cells, possibly through the operation of the membrane transport system. Its rate of production varies with the functional state of the tissue and it may play a role as an autocrine or paracrine mediator (e.g. controlling blood flow). The uptake of adenosine is blocked by dipyridamole, which has vasodilatory effects. The effects of adenosine are mediated by a group of G protein-coupled receptors (the Gi/o-coupled Ai- and A3 receptors, and the Gs-coupled A2a-/A2B receptors). Ai receptors can mediate vasoconstriction, block of cardiac atrioventricular conduction and reduction of force of contraction, bronchoconstriction, and inhibition of neurotransmitter release. A2 receptors mediate vasodilatation and are involved in the stimulation of nociceptive afferent neurons. A3 receptors mediate the release of mediators from mast cells. Methylxanthines (e.g. caffeine) function as antagonists of Ai and A2 receptors. Adenosine itself is used to terminate supraventricular tachycardia by intravenous bolus injection. 

This family contains more than 40 members subdivided into five subfamilies [4]. The NCS have been involved in phototransduction and regulation of neurotransmitter release. The NCS have two pairs of EF-hands and, unlike CaM and SI00 proteins, possess a consensus myristoylation sequence at the N-terminal responsible for the targeting of the NCS to the membrane. 

As to be expected from a peptide that has been highly conserved during evolution, NPY has many effects, e.g. in the central and peripheral nervous system, in the cardiovascular, metabolic and reproductive system. Central effects include a potent stimulation of food intake and appetite control [2], anxiolytic effects, anti-seizure activity and various forms of neuroendocrine modulation. In the central and peripheral nervous system NPY receptors (mostly Y2 subtype) mediate prejunctional inhibition of neurotransmitter release. In the periphery NPY is a potent direct vasoconstrictor, and it potentiates vasoconstriction by other agents (mostly via Yi receptors) despite reductions of renal blood flow, NPY enhances diuresis and natriuresis. NPY can inhibit pancreatic insulin release and inhibit lipolysis in adipocytes. It also can regulate gut motility and gastrointestinal and renal epithelial secretion. 

In squid giant axons, PbTx causes a depolarization of the plasma membrane, repetitive discharges followed by depression of action potentials, and a complete blockade of excitability. This action is antagonized by TTX (83,84). PbTx depolarizes nerve terminals and induces neurotransmitter release (85,86) it depolarizes skeletal muscle cells (87) and increases the frequency of action potentials in crayfish nerve cord (88). PbTx also produces a contraction of the guinea pig ileum (89). All these effects are prevented by TTX. 

The Effect of CXCR4-Mediated Signaling Pathway on Neuronal Activity and Neurotransmitter Release... 

Augustine GJ (2001) How does calcium trigger neurotransmitter release Curr Opin Neurobiol 11 320-326... 

Figure 1.6 Presynaptic inhibition of the form seen in the dorsal horn of the spinal cord, (a) The axon terminal (i) of a local neuron is shown making an axo-axonal contact with a primary afferent excitatory input (ii). (b) A schematic enlargement of the synapse, (c) Depolarisation of the afferent terminal (ii) at its normal resting potential by an arriving action potential leads to the optimal release of neurotransmitter, (d) When the afferent terminal (ii) is already partially depolarised by the neurotransmitter released onto it by (i) the arriving acting potential releases less transmitter and so the input is less effective...

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