Caffeine analogs: biomedical impact

Daly, John W.

doi:10.1007/s00018-007-7051-9

Cited by 233 publications

(238 citation statements)

References 152 publications

(134 reference statements)

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“…Caffeine modulates CNS activities through several mechanisms of action including antagonism of adenosine and GABA A receptors (Daly 2007), phosphodiesterase inhibition (Smellie et al 1979) and sensitization of calcium‐induced calcium release through ryanodine‐sensitive channels (McPherson et al 1991; Martín & Buño 2003). It has been suggested that, at the concentration typically consumed by humans, caffeine may act mainly by inhibiting adenosine receptors in the CNS (Fredholm 1995).…”

Section: Introductionmentioning

confidence: 99%

Caffeine‐mediated BDNF release regulates long‐term synaptic plasticity through activation of IRS2 signaling

et al. 2016

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Caffeine has cognitive‐enhancing properties with effects on learning and memory, concentration, arousal and mood. These effects imply changes at circuital and synaptic level, but the mechanism by which caffeine modifies synaptic plasticity remains elusive. Here we report that caffeine, at concentrations representing moderate to high levels of consumption in humans, induces an NMDA receptor‐independent form of LTP (CAFLTP) in the CA1 region of the hippocampus by promoting calcium‐dependent secretion of BDNF, which subsequently activates TrkB‐mediated signaling required for the expression of CAFLTP. Our data include the novel observation that insulin receptor substrate 2 (IRS2) is phosphorylated during induction of CAFLTP, a process that requires cytosolic free Ca2+. Consistent with the involvement of IRS2 signals in caffeine‐mediated synaptic plasticity, phosphorylation of Akt (Ser473) in response to LTP induction is defective in Irs2−/− mice, demonstrating that these plasticity changes are associated with downstream targets of the phosphoinositide 3‐kinase (PI3K) pathway. These findings indicate that TrkB‐IRS2 signals are essential for activation of PI3K during the induction of LTP by caffeine.

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Section: Introductionmentioning

confidence: 99%

Caffeine‐mediated BDNF release regulates long‐term synaptic plasticity through activation of IRS2 signaling

et al. 2016

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“…Caffeine has been used in pharmaceutical preparations as a neurological, cardiac and respiratory stimulant. It is also used as an analgesic enhancer in cold, cough and headache medicines (Daly, 2007). Other pharmaceutical applications of methylxanthines include use as a diuretic and a bronchodilator, and for relief of bronchial spasms and control of asthma (Daly, 2007).…”

Section: Introductionmentioning

confidence: 99%

“…It is also used as an analgesic enhancer in cold, cough and headache medicines (Daly, 2007). Other pharmaceutical applications of methylxanthines include use as a diuretic and a bronchodilator, and for relief of bronchial spasms and control of asthma (Daly, 2007). 1-Methylxanthine, 1-methyluric acid and uric acid have also been studied for their antioxidant properties (Lee, 2000).…”

Section: Introductionmentioning

confidence: 99%

Characterization of a broad-specificity non-haem iron N-demethylase from Pseudomonas putida CBB5 capable of utilizing several purine alkaloids as sole carbon and nitrogen source

Summers

Louie

et al. 2011

Microbiology

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N-Demethylation of many xenobiotics and naturally occurring purine alkaloids such as caffeine and theobromine is primarily catalysed in higher organisms, ranging from fungi to mammals, by the well-studied membrane-associated cytochrome P450s. In contrast, there is no well-characterized enzyme for N-demethylation of purine alkaloids from bacteria, despite several reports on their utilization as sole source of carbon and nitrogen. Here, we provide what we believe to be the first detailed characterization of a purified N-demethylase from Pseudomonas putida CBB5. The soluble N-demethylase holoenzyme is composed of two components, a reductase component with cytochrome c reductase activity (Ccr) and a two-subunit N-demethylase component (Ndm). Ndm, with a native molecular mass of 240 kDa, is composed of NdmA (40 kDa) and NdmB (35 kDa). Ccr transfers reducing equivalents from NAD(P)H to Ndm, which catalyses an oxygen-dependent N-demethylation of methylxanthines to xanthine, formaldehyde and water. Paraxanthine and 7-methylxanthine were determined to be the best substrates, with apparent K m and kcat values of 50.4±6.8 μM and 16.2±0.6 min−1, and 63.8±7.5 μM and 94.8±3.0 min−1, respectively. Ndm also displayed activity towards caffeine, theobromine, theophylline and 3-methylxanthine, all of which are growth substrates for this organism. Ndm was deduced to be a Rieske [2Fe–2S]-domain-containing non-haem iron oxygenase based on (i) its distinct absorption spectrum and (ii) significant identity of the N-terminal sequences of NdmA and NdmB with the gene product of an uncharacterized caffeine demethylase in P. putida IF-3 and a hypothetical protein in Janthinobacterium sp. Marseille, both predicted to be Rieske non-haem iron oxygenases.

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“…9,31,32 In most cases, the drug treatment raises the level of endogenous cAMP by blocking its hydorolysis, 32 and causes an imbalance of cAMP-signaling pathways involving G proteins and protein kinases. 33 This results in a serious alteration of physiological function.…”

Section: Discussionmentioning

confidence: 99%

Caffeine fostering of mycoparasitic fungi against phytopathogens

Sugiyama

Sano

Yazaki

et al. 2016

Plant Signaling & Behavior

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Abbreviation: PDA, potato dextrose agar Caffeine (1,3,7-trimethixanthine) is a typical purine alkaloid produced in more than 80 plant species. Its biological role is considered to strengthen plant's defense capabilities, directly as a toxicant to biotic attackers (allelopathy) and indirectly as an activator of defense system (priming). Caffeine is actively secreted into rhizosphere through primary root, and possibly affects the structure of microbe community nearby. The fungal community in coffee plant rhizosphere is enriched with particular species, including Trichoderma family, a mycoparasite that attacks and kills phytopathogens by coiling and destroying their hyphae. In the present study, the caffeine response of 8 filamentous fungi, 4 mycoparasitic Trichoderma, and 4 prey phytopathogens, was examined. Results showed that allelopathic effect of caffeine on fungal growth and development was differential, being stronger on pathogens than on Trichoderma species. Upon confronting, the prey immediately ceased the growth, whereas the predator continued to grow, indicating active mycoparasitism to have occurred. Caffeine enhanced mycoparasitism up to 1.7-fold. Caffeine thus functions in a double-track manner against fungal pathogens: first by direct suppression of growth and development, and second by assisting their natural enemy. These observations suggest that caffeine is a powerful weapon in the arms race between plants and pathogens by fostering enemy's enemy, and we propose the idea of "caffeine fostering" as the third role of caffeine.

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Caffeine analogs: biomedical impact

Cited by 233 publications

References 152 publications

Caffeine‐mediated BDNF release regulates long‐term synaptic plasticity through activation of IRS2 signaling

Caffeine‐mediated BDNF release regulates long‐term synaptic plasticity through activation of IRS2 signaling

Characterization of a broad-specificity non-haem iron N-demethylase from Pseudomonas putida CBB5 capable of utilizing several purine alkaloids as sole carbon and nitrogen source

Caffeine fostering of mycoparasitic fungi against phytopathogens

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