Biochemistry of Caffeine's Influence On Exercise Performance
Peter M. Tiidus, Rebecca E. K. MacPherson, Paul J. LeBlanc, Andrea R. Josse in The Routledge Handbook on Biochemistry of Exercise, 2020
As previously mentioned, caffeine is a non-specific adenosine receptor antagonist. Adenosine receptors are a group of G protein–coupled receptors that mediate the physiological actions of adenosine. There are four main subtypes of adenosine receptors (A1, A2A, A2B, and A3) classified by their differential coupling to adenylyl cyclase that regulate cyclic AMP (cAMP) levels (26, 69). Receptors are distributed throughout the body, with different tissues expressing specific subtypes. Adenosine A1 and A3 receptors are coupled to Gi/o proteins, while adenosine A2A and A2B receptors act upon Gs/olf proteins (25, 69). Binding of adenosine to its receptors results in changes in cAMP levels that initiate a host of cell responses, including ion channels and enzymes. Caffeine has a similar structure to adenosine and therefore binds to the same receptors, essentially blocking the normal effects of adenosine (antagonist). However, caffeine has different affinities for each type of adenosine receptor, explaining why caffeine can produce distinct impacts on tissues depending on the type and level of adenosine receptors present (Table 24.1).
Receptors and Signal Transduction Pathways Involved in Autonomic Responses
Kenneth J. Broadley in Autonomic Pharmacology, 2017
Caffeine is found in tea (Thea sinensis) and coffee (Coffea arabica), while cocoa contains theobromine and some caffeine. Another source of caffeine in the diet is from beverages based on cola flavouring, which contain extracts of cola nuts (Cola acuminata). The popularity of these caffeine-containing beverages is based upon the elevation of mood, decreased fatigue and increased capacity for work induced by the caffeine. Additionally, these non-selective PDE inhibitors have a wide range of peripheral pharmacological properties. They relax smooth muscle through elevation of cAMP and cGMP; these effects may be observed as bronchodilatation and vasodilatation of isolated blood vessels. Cardiac stimulation, diuresis and augmented secretion from exocrine and endocrine glands, particularly of gastric acid and pepsin, are further pharmacological actions of the methylxanthines. Blood pressure responses are variable but usually there is increased peripheral resistance and a rise in blood pressure, most likely due to release of catecholamines. The rise in blood pressure associated with caffeine consumption usually declines with chronic coffee drinkers. The pharmacological effects of the methylxanthines, as exemplified by theophylline, are not necessarily due to PDE inhibition and therefore a complete analysis of its mechanism of action is not warranted here. Additionally, theophylline is an adenosine receptor antagonist and is an inhibitor of intracellular Ca2+ mobilization.
The Role of Endogenous Sleep-promoting Substances
Clete A. Kushida in Sleep Deprivation, 2004
A number of studies demonstrate that systemic or intracerebroventricular injection of adenosine or locally infused adenosine into the basal forebrain increases the time spent in rapid-eye-movement (REM) and non-REM (NREM) sleep, and electroencephalographic (EEG) slow-wave activity during NREM sleep. In contrast, A1 antagonists decrease sleep (reviewed in Ref. 13). Interestingly, adenosine stimulates and caffeine (an adenosine receptor antagonist) or selective A1 antagonists inhibit rest in Drosophila, although adenosine receptors are not known in this insect (15). Less sleep time and decreases in the EEG slow-wave response to sleep deprivation were reported in A1 receptor knockout mice (16). However, other experiments suggested that sleep deficits did not occur in A1 knockout mice thoroughly adapted to the recording conditions (17). Chronic loss of adenosine action, therefore, might be compensated by other means of sleep regulation.
Borneol and Α-asarone as adjuvant agents for improving blood–brain barrier permeability of puerarin and tetramethylpyrazine by activating adenosine receptors
Published in Drug Delivery, 2018
Jun-Yong Wu, Yong-Jiang Li, Le Yang, Yi-Yun Hu, Xiong-Bin Hu, Tian-Tian Tang, Jie-Min Wang, Xin-Yi Liu, Da-Xiong Xiang
PUE, TMP, strychnine (STR) and phenobarbital (PB) were purchased from the National Institute for the Control of Pharmaceutical and Biological Products (Beijing, China). Acetonitrile and formic acid (HPLC grade) were purchased from Merck KGaA (Darmstadt, Germany) and ROE scientific Inc. (Newark, USA). Borneol, α-asarone, selective A1 adenosine receptor antagonist (DPCPX), A2A adenosine receptor antagonist (SCH58261) were purchased from Sigma-Aldrich (St. Louis, MO, USA). CD73 inhibitor adenosine 5′-( α, β-methylene) diphosphate sodium salt (APCP) was purchased from Bio-Techne China Co. Ltd (Shanghai, China). Dulbecco’s modified Eagle medium (DMEM), Fetal bovine serum (FBS), Penicillin-Streptomycin solution and Trypsin-EDTA solution were purchased from Gibco (Tulsa, OK, USA). Water was purified and demonized by Milli-Q ultrapure water purifications system.
Diaphragmatic recovery in rats with cervical spinal cord injury induced by a theophylline nanoconjugate: Challenges for clinical use
Published in The Journal of Spinal Cord Medicine, 2019
Fangchao Liu, Yanhua Zhang, Janelle Schafer, Guangzhao Mao, Harry G. Goshgarian
Theophylline (1, 3-dimethylxanthine), a methylxanthine, acting as a bronchodilator, has been clinically prescribed to treat symptoms of asthma, bronchitis, and emphysema.1,2 Specifically, theophylline has been shown to enhance respiratory drive by acting as an adenosine receptor antagonist3–5 that blocks both A1 and A2 adenosine receptors.6 In C2Hx (C2 hemisected) injured rats, systemic (oral or intravenous) administration of theophylline stimulates the CPP, which activates phrenic motoneurons ipsilateral to the hemisection (Fig. 1), by increasing respiratory output; this results in recovery of function of both the phrenic nerve and diaphragm.6,7 Theophylline-induced return of diaphragm function can be transient or permanent based on the number and frequency of doses (Nantwi et al.,6 1x intravenous; Nantwi et al.,8 multiple oral doses).
Beetroot supplemented diet exhibit anti-amnesic effect via modulation of cholinesterases, purinergic enzymes, monoamine oxidase and attenuation of redox imbalance in the brain of scopolamine treated male rats
Published in Nutritional Neuroscience, 2022
Tosin A. Olasehinde, Sunday I. Oyeleye, Collins U. Ibeji, Ganiyu Oboh
The result obtained in this study also revealed that there was an increase in ADA activity in the brain of untreated SCOP-administered male rats. ADA is important in the regulation of adenosine in the synaptic cleft; therefore, its upregulation may lead to rapid hydrolysis and depletion of adenosine [52]. Moreover, low levels of adenosine have been linked with disruption of memory function in AD [53]. In this study, the consumption of BRSD prevented an undue increase in ADA activity induced by SCOP-administration. This result is consistent with the report of Guttieres et al. [7], which revealed that SCOP triggered an increase in ADA activity, hence may alter adenosinergic neurotransmission by depleting extracellular levels of adenosine. Moreover, high ADA activity leads to a significant decrease in adenosine levels and has been linked with impaired memory function. This is because adenosine plays an important role in neuronal plasticity [54] and modulates long term depression and low term potentiation in the brain, which is associated with memory function and learning activities [55]. The observed decrease in ADA activity exhibited by BRSD fed rats may lead to an improvement in adenosinergic neurotransmission by increasing adenosine levels, which has been shown to play a protective role against memory impairment via its interaction with adenosine receptors [56]. Moreover, alterations in homeostatic levels of adenosine have been implicated in the disruption of adenosine receptors (A1AR and A2AR), which leads to loss of synaptic function and memory impairment [57]. Hence compounds capable of acting as adenosine receptor antagonist may prevent neuronal dysfunction and cognitive impairment.
Related Knowledge Centers
- Adenosine Receptor
- Adenosine Receptor Agonist
- Caffeine
- Receptor Antagonist
- Theobromine
- Theophylline
- Drug
- Isam-140
- Adenosine Reuptake Inhibitor