Stimulation of neurotransmitter release

Iwasaki S, Kataoka M, Sekiguchi M et al (2000) Two distinct mechanisms underlie the stimulation of neurotransmitter release by phorbol esters in clonal rat pheochromocytoma PC 12 cells. J Biochem (Tokyo) 128 407-14... 

Maidhood L, Saith I, Hsiao TH, et al. 1985. Leptinotoxin-h action in synaptosomcs and neurosecretory cells Stimulation of neurotransmitter release. J Neurochem 45 1719-1730. 

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. 

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. 

The role of the nervous system in pheromone biosynthesis in moths is not clearly understood. Christensen and co-workers [208-211] proposed that the neurotransmitter octopamine may be involved as an intermediate messenger during the stimulation of sex pheromone production in H. virescens. These workers suggested that octopamine was involved in the regulation of pheromone production and that PBAN s role lies in the stimulation of octopamine release at nerve endings. However, contradicting results concerning octopa-mine-stimulated pheromone production were reported in the same species as well as other moth species [163,172,212-214]. 

Figure 3.3 Ritalin works by affecting the communication between neurons and the neurotransmitters serotonin, dopamine, and norepinephrine. Ritalin and other stimulants increase the number of neurotransmitters released into the synapses (the spaces between individual neurons) and help keep the neurotransmitters in the synapse longer than they would remain without the drugs. This diagram demonstrates the flow of neurotransmitters between neurons, across a synapse.

As discussed above, two of the established effectors of the Ga limb of heterotrimeric G-proteins are adenylate cyclase (AC) and phospholipase C (PLCP), which, on stimulation, lead to the generation of the second-messenger molecules, cAMP and DAG/IP3, respectively. Through the respective activation of cAMP-dependent protein kinase (PKA) and Ca2+/phospholipid-dependent protein kinase (PKC), GPCRs coupled to AC and PLCp have the potential to effect indirect modulation of neurotransmitter release by phosphorylation of substrate proteins involved in the... 

Ferkany JW, Zaczek R, Coyle JT (1982) Kainic acid stimulates excitatory amino acid neurotransmitter release at presynaptic receptors. Nature 298 757-9 Fink K, Gothert M, Molderings G, Schlicker E (1989) N-methyl-D-aspartate (NMDA) receptor-mediated stimulation of noradrenaline release, but not release of other neurotransmitters, in the rat brain cortex receptor location, characterization and desensitization. Naunyn Schmiede-berg s Arch Pharmacol 339 514-21... 

Photoexcited rhodopsin activates transducin, a G-protein, which in turn stimulates cyclic GMP phosphodiesterase this leads to closing of an ion channel, hyperpolarization of the membrane, and a decreased rate of neurotransmitter release (Wald, 1968 Stryer, 1986 Chabre and Deterre, 1989). 

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