Adenosine neuromodulators

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Lauro C, Di Angelantonio S, Cipriarri R et al (2008) Activity of adenosine receptors type 1 is required for CX3CLl-mediated neuroprotection and neuromodulation in hippocampal neurons. J Immunol 180 7590-7596... 

Adenosine is not a classical neurotransmitter because it is not stored in neuronal synaptic granules or released in quanta. It is generally thought of as a neuromodulator that gains access to the extracellular space in part from the breakdown of extracellular adenine nucleotides and in part by translocation from the cytoplasm of cells by nucleoside transport proteins, particularly in stressed or ischemic tissues (Fig. 17-2C). Extracellular adenosine is rapidly removed in part by reuptake into cells and conversion to AMP by adenosine kinase and in part by degradation to inosine by adenosine deaminases. Adenosine deaminase is mainly cytosolic but it also occurs as a cell surface ectoenzyme. 

The inhibitory neuromodulator, adenosine, is considered to be a major candidate for a sleep-inducing factor. Systemic or intracerebroventricular injec-... 

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The drug of choice for most Americans is caffeine. In fact, caffeine is the most widely used psychoactive drug in the world. Many of caffeine s effects are believed to occur because of competitive antagonism at adenosine receptors. Adenosine is a neuromodulator that influences a number of functions in the CNS. The mild sedating... 

The endogenous purine mediator adenosine, originating from adenosine 5-triphosphate (ATP), is a widely distributed neuromodulator with complex effects (Sawynok, 1998 Sawynok and Liu, 2003). Four adenosine receptors have been identified and are termed Al, A2A, A2B, and A3 (Fredholm et al., 2001). They are all GPCRs and couple to classical second messenger pathways Al and A3 receptor activation decreases the level of cAMP, A2 increases it, whereas A2B receptor stimulates PLC (Sawynok, 1998 Sawynok and Liu, 2003). 

Hypoxia is an integral part of ischemia and plays a vital role in its pathophysiology. Hypoxia inducible factor (HIF-1) mediates transcription of several genes. Activation of HIF-1 also stimulates the production of VEGF, erythropoietin, bFGF, and other factors associated with neovascularization (Semenza, 2000 Maxwell and RatcHffe, 2002 Vincent et al., 2002). Another potential factor for neovascularization is adenosine, a neuromodulator that can act on specific receptors (putatively A2A and A2B receptors) on the endothelial cells, and through nitric oxide mediation it can stimulate cell migration and tube formation (Lutty and Mcleod, 2003). 

Caffeine Caffeine, a mild stimulant, is the most widely used psychoactive drug in the world. It is present in soft drinks, coffee, tea, cocoa, chocolate, and numerous prescription and over-the-counter drugs. It mildly increases NE and DA release and enhances neural activity in numerous brain areas. Caffeine is absorbed from the digestive tract and is distributed rapidly throughout all tissues and easily crosses the placental barrier see Chapter 27). Many of caffeine s effects are beheved to occur by means of competitive antagonism at adenosine receptors. Adenosine is a neuromodulator that influences a number of functions in the CNS see Chapters 12 and 27). The mild sedating effects that occur when adenosine activates particrrlar adenosine-receptor subtypes can be antagonized by caffeine. 

Many of these effects can be explained by an interference with a central signal cascade (Fig. 5.195). Adrenaline activates adenylylcyclase, which converts adenosine triphosphate (ATP) into cyclic 3 ,5 -adenosine monophosphate (cAMP). This is a secondary messenger, which is deactivated by a phosphodiesterase to adenosine monophosphate (AMP). Dephosphorylation with a 5 -nucleotidase releases the neuromodulator adenosine, which is enriched extracellularly in the waking state and is degraded during sleep. When adenosine binds in the presynaptic cleft to adenosine-Aj-receptors of the nerve cells, the release of most neurotransmitters, like glutamate, y-aminobutyric acid, norephedrine, serotonin and acetylcholine is inhibited. In addition, adenosine inhibits adenylylcyclase. 

Figueira and Ribeiro (23) used silica gel separations of noncyclic radioactive [H ] adenosine as neuromodulators, and reduced from 2-D to 1-D. The solvents were varieties of butanol-ammonia-water-acetic acid. Rapidity of separation occurred in 3-4 h. Typical separations unequivocally demonstrated cAMP, inosine, adenosine, and adenine. UV sensitivity occurred at S nmol. Paces and Kaminek (24) separated plant cytokinins (adenine) on silica gel in ethanol-ammonium borate butanol-ammonia butanol-water. Norman et al. (25) measured ATP from degraded meat via 5% cold PCA on silica gel and isobutanol-amyl alcohol-ethoxyethanol-ammonia-water. 

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