A Drosophila adenosine receptor activates cAMP and calcium signaling

Doleželová, Eva; Nothacker, Hans‐Peter; Civelli, Olivier; Bryant, Peter J.; Z̆urovec, Michal

doi:10.1016/j.ibmb.2006.12.003

Cited by 69 publications

(91 citation statements)

References 35 publications

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“…Because both specific and nonspecific adenosine antagonists led to similar behavioral consequences, this suggests that the wake-promoting effects of CAFF are mediated by adenosine receptors. Because a single adenosine receptor (AdoR), a likely counterpart of the A2B receptor in mammals, has been described in Drosophila (15), the arousing effects of adenosine receptor antagonists and CAFF are most likely mediated by the same AdoR.…”

Section: Adenosinergic and Dopaminergic Systems Mediate Wake-promotingmentioning

confidence: 99%

Drosophila D1 dopamine receptor mediates caffeine-induced arousal

Andretic

Kim

Jones

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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The arousing and motor-activating effects of psychostimulants are mediated by multiple systems. In Drosophila, dopaminergic transmission is involved in mediating the arousing effects of methamphetamine, although the neuronal mechanisms of caffeine (CAFF)-induced wakefulness remain unexplored. Here, we show that in Drosophila, as in mammals, the wake-promoting effect of CAFF involves both the adenosinergic and dopaminergic systems. By measuring behavioral responses in mutant and transgenic flies exposed to different drug-feeding regimens, we show that CAFFinduced wakefulness requires the Drosophila D1 dopamine receptor (dDA1) in the mushroom bodies. In WT flies, CAFF exposure leads to downregulation of dDA1 expression, whereas the transgenic overexpression of dDA1 leads to CAFF resistance. The wakepromoting effects of methamphetamine require a functional dopamine transporter as well as the dDA1, and they engage brain areas in addition to the mushroom bodies.ptimal behavioral performance in humans and animals depends on an adequate arousal level, which often involves diffuse afferent inputs from the dopaminergic system. Caffeine (CAFF) displays strong arousing properties and is the most consumed psychoactive drug in the world. CAFF competitively inhibits adenosine A1 and A2 receptors, antagonizing the effects of the sleep-promoting neuromodulator adenosine that accumulates during waking (1). CAFF also leads to increased dopaminergic and glutamatergic transmission in different striatal subcompartments, which has been linked to its activating and reinforcing effects (2-4).Although CAFF-induced wakefulness has been related to modulation of cholinergic and histaminergic arousal systems (5, 6), CAFF's induction of increased dopaminergic transmission and its effect on wakefulness have not been adequately examined. Animals with increased dopaminergic transmission, such as dopamine transporter (DAT) mutant mice, have decreased non-rapid eye movement sleep and increased sensitivity to the wake-promoting action of CAFF (7). Dopaminergic action on both the D1 and D2 receptors contributes to the alert waking state, based on the action of centrally administered D1 and D2 agonists in rodents (8). Molecularly, CAFF modulates D2 transcription in vitro and in vivo (9). Motor-activating effects of CAFF are diminished in D2R mutant mice (10, 11); however, the role of D2R in the arousing effect of CAFF remains unknown, and functional tests of the brain regions mediating these effects are lacking in mammals.We have shown previously that the wake-promoting effects of methamphetamine (METH) in Drosophila are mediated through dopaminergic transmission, indicating some evolutionary conservation in the behavioral and neurochemical effects of psychostimulants (12).Treatment of flies with CAFF induces wakefulness; however, the mechanism underlying this activity is currently unknown (13,14). In the present study, we investigate the role of dopamine signaling in the wake-inducing properties of CAFF and METH, with emphasis on the role of the Dr...

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Section: Adenosinergic and Dopaminergic Systems Mediate Wake-promotingmentioning

confidence: 99%

Drosophila D1 dopamine receptor mediates caffeine-induced arousal

Andretic

Kim

Jones

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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“…Although AdoR expression was previously observed using in situ hybridization in the ring gland where AKH-producing cells are also located, it was not detected in the fat body (Dolezelova et al, 2007). However, the AdoR expression was very weak, producing faint signals.…”

Section: Disease Models and Mechanisms 777mentioning

confidence: 75%

“…Because AdoR is expressed in the Drosophila ring gland (Dolezelova et al, 2007) where the AKH-producing cells are located (Lee and Park, 2004;Isabel et al, 2005), we speculated that the effect of adenosine could be triggered by AKH release in response to AdoR signaling in the ring gland. However, the ablation of AKH-producing cells did not rescue the adgf-a mutant, which demonstrates that AKH is not involved in the observed effect of adenosine on carbohydrate metabolism.…”

Section: Dmmbiologistsorg 780mentioning

confidence: 99%

“…Drosophila possesses one homolog of the adenosine receptor (AdoR) (Dolezelova et al, 2007), which activates cAMP and calcium signaling similarly to mammalian A2B receptor by coupling to the G-protein subunitsG s and G q . A rescue of the adgf-a mutant phenotype by the adoR mutation showed that a significant part of the mutant phenotype is caused by the signaling effect of the extracellular adenosine .…”

Section: Introductionmentioning

confidence: 99%

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Increased extracellular adenosine in Drosophila that are deficient in adenosine deaminase activates a release of energy stores leading to wasting and death

Zuberova

Fencková

Šimek

et al. 2010

Disease Models &Amp; Mechanisms

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SUMMARYExtracellular adenosine is an important signaling molecule in neuromodulation, immunomodulation and hypoxia. Adenosine dysregulation can cause various pathologies, exemplified by a deficiency in adenosine deaminase in severe combined immunodeficiency. We have established a Drosophila model to study the effects of increased adenosine in vivo by mutating the main Drosophila adenosine deaminase-related growth factor (ADGF-A). Using a genetic screen, we show here that the increased extracellular adenosine in the adgf-a mutant is associated with hyperglycemia and impairment in energy storage. The adenosine works in this regard through the adenosine receptor as an anti-insulin hormone in parallel to adipokinetic hormone, a glucagon counterpart in flies. If not regulated properly, this action can lead to a loss of energy reserves (wasting) and death of the organism. Because adenosine signaling is associated with the immune response and the response to stress in general, our results mark extracellular adenosine as a good candidate signal involved in the wasting syndrome that accompanies various human pathologies.

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“…Notably, activation of adenosine receptors located at nerve terminals inhibits transmitter release (Fredholm et al, 1999;Dunwiddie and Masino, 2001;Tomás et al, 2014). In insects, adenosine receptors have been identified in Drosophila (Dolezelova et al, 2007); however, their amino acid sequences are somewhat different from those in mammals. The physiological function of insect adenosine receptors remains unclear (Mustard, 2014).…”

Section: Discussionmentioning

confidence: 99%

Effects of Caffeine on Olfactory Learning in Crickets

et al. 2016

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Caffeine is a plant-derived alkaloid that is generally known as a central nervous system (CNS) stimulant. In order to examine the effects of caffeine on higher CNS functions in insects, we used an appetitive olfactory learning paradigm for the cricket Gryllus bimaculatus. Crickets can form significant long-term memories (LTMs) after repetitive training sessions, during which they associate a conditioned stimulus (CS: odor) with an unconditioned stimulus (US: reward). Administration of hemolymphal injections of caffeine established LTM after only single-trial conditioning over a wide range of caffeine dosages (1.6 μ μg/kg to 39 mg/kg). We investigated the physiological mechanisms underlying this enhancement of olfactory learning performance pharmacologically, focusing on three major physiological roles of caffeine: 1) inhibition of phosphodiesterase (PDE), 2) agonism of ryanodine receptors, and 3) antagonism of adenosine receptors. Application of drugs relevant to these actions resulted in significant effects on LTM formation. These results suggest that externally applied caffeine enhances LTM formation in insect olfactory learning via multiple cellular mechanisms.

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A Drosophila adenosine receptor activates cAMP and calcium signaling

Cited by 69 publications

References 35 publications

Drosophila D1 dopamine receptor mediates caffeine-induced arousal

Drosophila D1 dopamine receptor mediates caffeine-induced arousal

Increased extracellular adenosine in Drosophila that are deficient in adenosine deaminase activates a release of energy stores leading to wasting and death

Effects of Caffeine on Olfactory Learning in Crickets

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