11/30/2023 0 Comments Adenosine caffeine structure![]() ![]() (c) during daily repeated caffeine intake, the adenosine system may adapt to the daily presence of the stimulant. Black triangles denote frequency bins in which power density after caffeine intake significantly differed from placebo ( p < 0.05, paired t tests). (b) Typical reduction of SWA and increased sigma frequency activity in NREM sleep after acute caffeine intake (data from Landolt, Dijk, et al., 1995). ![]() Beside caffeine itself, paraxanthine may therefore contribute to the wake‐promoting potential. There is evidence in the animal domain that caffeine's main metabolite paraxanthine has similar affinity as caffeine (Snyder et al., 1981) to both receptors (Chou & Vickroy, 2003) and disturbs NREM sleep (Okuro et al., 2010). (a) Approximately 30 min after oral intake, caffeine reaches the central nervous system and blocks adenosine A 1 and A 2A receptors. Simplified illustration of the impact of caffeine intake in the brain. 5′‐ENs, 5′‐ecto‐nucleotidases 5′‐N, 5′‐nucleotidase A 1, A 2A, adenosine A 1 and A 2A receptors AC, adenylyl cyclase ADA, adenosine deaminase AdK, adenosine kinase Ado, adenosine (red dots) ADP, adenosine diphosphate AMP, adenosine monophosphate CaMKII, Ca 2+/calmodulin‐dependent protein kinase II cAMP, cyclic adenosine monophosphate CCPA, 2‐chloro‐N 6‐cyclopentyladenosine CPA, N 6‐cyclopentyladenosine CREB, cAMP responsive element binding protein D 2, dopamine D 2 receptor DAG, diacyl‐glycerol EEG, electroencephalography ENT, equilibrative nucleoside transporters ER, endoplasmic reticulum Glu, glutamate (blue dots) Ino, inosine IP 3, inositol‐tri‐phosphate mGluR5, metabotropic glutamate receptor of subtype‐5 PKC, PKA, protein kinase C and A SAH, S‐adenosyl‐homocysteine SAHH, S‐adenosyl‐homocysteine hydrolase The unique co‐localisation and functional interactions among the G‐protein coupled adenosine (red), dopamine (green) and metabotropic glutamate receptors (blue) on striato‐pallidal neurones and circuits suggest a hypothesised integration of adenosine‐dopamine‐glutamate signalling and synaptic plasticity. Neurones, astrocytes, and microglia can release adenosine and adenosine triphosphate (ATP). Only selected processes and pathways mentioned in the text are shown (please see text for more detailed information). Simplified schematic representation of adenosine formation, transport and metabolism in a hypothetical tripartite synapse consisting of a presynaptic terminal, a postsynaptic spine, and an astrocyte. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society. We conclude our review by highlighting some open questions that need to be answered, to better understand how adenosine and caffeine exactly regulate and influence sleep.Ĭhronic caffeine circadian genetics sleep deprivation sleep homeostasis sleep-wake disorder. In the final section, we discuss the perspectives of possible clinical applications of the accumulated knowledge over the last century that may improve sleep-related disorders. In addition, we review the more recent evidence that adenosine levels may also influence the functioning of the circadian clock and address the question of whether sleep homeostasis and the circadian clock may interact through adenosinergic signalling. We critically investigate the evidence for a direct involvement in sleep homeostatic mechanisms and whether the effects of caffeine on sleep differ between acute intake and chronic consumption. In this review, we discuss the current state of the science in model organisms and humans on the working mechanisms of adenosine and caffeine on sleep. Today, adenosine is widely accepted as an endogenous sleep-regulatory substance. Since the scientific demonstration that this is indeed the case, progress has been fast. About 70 years ago, adenosine itself entered the picture as a possible ligand of the receptors where caffeine hooks on as an antagonist to reduce sleepiness. For ~100 years now, systematic research has been performed, first started by testing the effects of different dosages of caffeine on sleep and waking behaviour. For hundreds of years, mankind has been influencing its sleep and waking state through the adenosinergic system. ![]()
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