Biphasic effect of methylxanthines on acetylcholine release from electrically‐stimulated brain slices

Pedata, Felicita; Pepeu, Giancarlo; Spignoli, G.

doi:10.1111/j.1476-5381.1984.tb10120.x

Cited by 33 publications

(8 citation statements)

References 21 publications

(24 reference statements)

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“…Although caffeine is a benzodiazepine receptor antagonist, this property is only present at toxic levels of plasma caffeine (File et al, 1982) and cannot explain the effects observed in the present study. Recent research suggests that antagonism of adenosine A(2a) receptors (Pedata et al, 1984;Varani et al, 2000;Scammell et al, 2001) or an increase in sympathetic activation/catecholamines (Kamimori et al, 2000) may be involved.…”

Section: Discussionmentioning

confidence: 99%

Caffeine Reversal of Ethanol Effects on the Multiple Sleep Latency Test, Memory, and Psychomotor Performance

Drake

Roehrs

Turner

et al. 2002

Neuropsychopharmacol

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Caffeine has been shown to reverse some of the performance-impairing effects of ethanol. However, it is not known whether this antagonistic effect of caffeine is mediated by a reduction in sleepiness. The present study assessed physiological alertness/sleepiness, memory, and psychomotor performance following the administration of placebo, ethanol, and caffeine+ethanol combinations. A total of 13 healthy individuals (21-35 years old) underwent four conditions presented in a Latin Square Design: placebo-placebo, ethanol (0.5 g/kg)-placebo, ethanol (0.5 g/kg)-caffeine 150 mg, and ethanol (0.5 g/kg)-caffeine 300-mg. The Multiple Sleep Latency Test (MSLT), psychomotor performance battery, memory test, and mood/sleepiness questionnaires were administered following each condition. The peak breadth ethanol concentration (BrEC) was 0.043+/-0.0197% and did not differ among the three caffeine treatments. As expected, ethanol reduced mean latency on the MSLT. The lowest caffeine dose reversed this effect and the highest dose increased mean latency (greater alertness) significantly beyond placebo levels. Ethanol also impaired psychomotor performance and memory. The 300-mg caffeine dose restored performance and memory measures to placebo levels. Although visual analog ratings of dizziness were increased by ethanol, they were not diminished by either caffeine dose. In conclusion, Low-dose caffeine prevented the sleepiness and performance impairment associated with a moderate dose of ethanol. Thus, caffeine, similar to other stimulants, can reverse the physiologically sedating effects of ethanol, although other negative effects remain.

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Section: Discussionmentioning

confidence: 99%

Caffeine Reversal of Ethanol Effects on the Multiple Sleep Latency Test, Memory, and Psychomotor Performance

Drake

Roehrs

Turner

et al. 2002

Neuropsychopharmacol

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“…Both effects appear to involve purine receptors (Pedata et al, 1984). It is therefore difficult to account for their disappearance, the unchanged effect of adenosine and the increase in the A1 receptor high affinity subtype.…”

Section: Discussionmentioning

confidence: 99%

“…Caffeine, added to the superfusing solution at the concentration of 50 piM enhances acetylcholine (ACh) release. Conversely, at a concentration of 0.5 mM caffeine decreases ACh release (Pedata et al, 1984).…”

Section: Introductionmentioning

confidence: 99%

Chronic caffeine treatment reduces caffeine but not adenosine effects on cortical acetylcholine release

Corradetti

Pedata

Pepeu

et al. 1986

British J Pharmacology

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The effects of both adenosine and caffeine on the release of acetylcholine (ACh) were investigated in slices of cerebral cortex taken from rats pretreated for 30 days with caffeine (100 mg kg−1 daily, dissolved in their drinking water) at rest and during electrical stimulation at frequencies of 0.2, 1 and 5 Hz. The effect of this treatment on adenosine binding sites was also investigated in cortical membranes using N‐cyclohexyl‐(3H]‐adenosine ([3H]‐CHA) as a ligand. The chronic caffeine treatment did not change animal growth patterns. Spontaneous exploratory activity appeared to be increased at the 3rd day but was unchanged at the 30th day when compared with controls. Caffeine‐treatment increased the number of high affinity binding sites for [3H]‐CHA by 64% over the control values. Low affinity binding site density and affinity constants were unaffected. Adenosine 30 μM added to the superfusion fluid decreased electrically stimulated ACh release both in rats drinking tap water and rats drinking caffeine. In rats drinking tap water, caffeine added to the superfusion fluid at a concentration of 50 μM enhanced ACh release, while at 0.5 mM it decreased ACh output from the slices. Both effects were abolished by pretreatment with caffeine in vivo. The results indicate that prolonged consumption of high doses of caffeine causes changes in the responsiveness of cholinergic neurones to caffeine. The change is not shared by adenosine, through whose recognition sites caffeine is believed to act. It is therefore possible that the adaptive changes following repeated caffeine administration involve either only the coupler‐transducer mechanism activated by the antagonist, or effects unrelated to receptors.

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“…Opposite effects from A 1 -mediated synaptic inhibition are elicited by A 2A receptor activation, which has been shown to mediate excitatory actions in synaptic function [ 62 – 64 ]. In the hippocampus in vitro, A 2A receptor stimulation results in a Ca 2+ -dependent release of acetylcholine [ 65 , 66 ].…”

Section: Role Of Adenosine In Cerebral Transmission Under Normoxic Comentioning

confidence: 99%

The role of ATP and adenosine in the brain under normoxic and ischemic conditions

Pedata

Melani

Pugliese

et al. 2007

Purinergic Signalling

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By taking advantage of some recently synthesized compounds that are able to block ecto-ATPase activity, we demonstrated that adenosine triphosphate (ATP) in the hippocampus exerts an inhibitory action independent of its degradation to adenosine. In addition, tonic activation of P2 receptors contributes to the normally recorded excitatory neurotransmission. The role of P2 receptors becomes critical during ischemia when extracellular ATP concentrations increase. Under such conditions, P2 antagonism is protective. Although ATP exerts a detrimental role under ischemia, it also exerts a trophic role in terms of cell division and differentiation. We recently reported that ATP is spontaneously released from human mesenchymal stem cells (hMSCs) in culture. Moreover, it decreases hMSC proliferation rate at early stages of culture. Increased hMSC differentiation could account for an ATP-induced decrease in cell proliferation. ATP as a homeostatic regulator might exert a different effect on cell trophism according to the rate of its efflux and receptor expression during the cell life cycle. During ischemia, adenosine formed by intracellular ATP escapes from cells through the equilibrative transporter.

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Biphasic effect of methylxanthines on acetylcholine release from electrically‐stimulated brain slices

Abstract: On the other hand the mechanism through which methylxanthines decrease ACh release remains obscure.

Cited by 33 publications

References 21 publications

Caffeine Reversal of Ethanol Effects on the Multiple Sleep Latency Test, Memory, and Psychomotor Performance

Caffeine Reversal of Ethanol Effects on the Multiple Sleep Latency Test, Memory, and Psychomotor Performance

Chronic caffeine treatment reduces caffeine but not adenosine effects on cortical acetylcholine release

The role of ATP and adenosine in the brain under normoxic and ischemic conditions

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