Adenosine and sleep

Porkka-Heiskanen, T., Alanko, L., Kalinchuk, A., Stenberg, D. (2002). Adenosine and sleep. Sleep Med. Revis 6, 321-32. 

Basheer, R., et al. (2004). Adenosine and sleep-wake regulation. Prog. Neurobiol. 73, 79-96. 

Basheer R, Strecker RE, Thakkar MM, Me Carley RW (2004) Adenosine and sleep-wake regulation. Progr Neurobiol 73 379-396... 

Coleman, C. G., Baghdoyan, H. A. 8r Lydic, R. (2006). Dialysis delivery of an adenosine A2A agonist into the pontine reticular formation of C57BL/6J mouse increases pontine acetylcholine release and sleep. J. Neurochem. 96, 1750-9. 

Adenosine has been proposed to induce sleep by inhibiting cholinergic neurons of the BFB and the brainstem. In this respect, adenosine and the adenosine transport inhibitor NBTI decrease the discharge rate of BFB neurons during W, whereas the adenosine Ai receptor antagonist CPDX induces the opposite effects (Alam et al., 1999 Strecker et al., 2000). In addition, perfusion of adenosine into... 

Sleep-active neurons have been identified in the ventrolateral and medial preoptic areas. These neurons exhibit increased discharge during SWS and REMS rather than W. Sleep-active neurons colocalize GABA and are excited by adenosine and prostaglandin D2 (McGinty Szymusiak, 2001) (Table 9.3). 

Pharmacological experiments have shown that adenosine and its receptor agonists promote, whereas its antagonists inhibit, sleep. Early experiments showed that injection into the cerebral ventricles of 2 pmol (0.5 mg) adenosine... 

Despite theoretical and experimental indications that adenosine has hypno-genic effects, it was necessary, in order to postulate adenosine as a homeostatic sleep factor, to show that its concentration in vivo depends on previous wakefulness and sleep, and to explain the mechanism of its hypnogenic effect. 

Radulovacki, M., Virus, R. M., Rapoza, D. Crane, R. A. (1985). A comparison of the dose response effects of pyrimidine ribonucleosides and adenosine on sleep in rats. Psychopharmacology 87 (2), 136-40. 

The importance of adenosine deaminase in the duration and intensity of sleep in humans has been noted recently (Retey et al. 2005). Animal studies suggest that sleep needs are genetically controlled, and this also seems to apply in humans. Probably, a genetic variant of adenosine deaminase, which is associated with the reduced metabolism of adenosine to inosine, specifically enhances deep sleep and slow wave activity during sleep. Thus low activity of the catabolic enzyme for adenosine results in elevated adenosine, and deep sleep. In contrast, insomnia patients could have a distinct polymorphism of more active adenosine deaminase resulting in less adenosine accumulation, insomnia, and a low threshold for anxiety. This could also explain interindividual differences in anxiety symptoms after caffeine intake in healthy volunteers. This could affect the EEG during sleep and wakefulness in a non-state-specific manner. 

Radulovacki M., Virus R. M., Djuricic-Nedelson M., Green R. D. (1984). Adenosine analogs and sleep in rats. J. Pharmacol. Exp. Ther. 228, 268-74. 

Adenosine and inosine can be transported across cell membranes in either direction, facilitated by a membrane-associated nucleoside transport protein. Concentrative transporters have also been identified. Messenger RNA for a pyrimidine-selective Na+-nucleoside cotransporter (rCNTl) and a purine-selective Na+-nucleoside cotransporter (rCNT2) are found throughout the rat brain. Most degradation of adenosine is intracellular, as evidenced by the fact that inhibitors of adenosine transport, such as dipyridamole, increase interstitial levels of adenosine. Dipyridamole is used clinically to elevate adenosine in coronary arteries and produce coronary vasodilation. In high doses, dipyridamole can accentuate adenosine-receptor-mediated actions in the CNS, resulting in sedation and sleep, anticonvulsant effects, decreased locomotor activity and decreased neuronal activity. 

Adenosine 2a receptor ADORA2A Agonism Inhibition of platelet aggregation, anti-inflammation and neuroprotective effects, coronary vasodilation, decreased blood pressure, increased plasma renin activity and sleep induction. Antagonism Increased platelet aggregation, hypertension, nervousness (tremor, agitation), arousal, insomnia, cerebral and coronary vasodilation (in microvessels only). 

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