Interaction of caffeine with the GABAA receptor complex: alterations in receptor function but not ligand binding

Lopez, Fred; Miller, Lawrence G.; Greenblatt, David J.; Kaplan, Gary B.; Shader, Richard I.

doi:10.1016/0922-4106(89)90028-x

Cited by 50 publications

(29 citation statements)

References 21 publications

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“…Studies on the effects of methylxanthines on benzodiazepine receptors are contradictory. An increased number of benzodiazepine binding sites in the adult mouse brain after chronic administration of a high dose of caffeine has been reported (17,18), but other investigators have shown no change at all (19,20) or altered function of the receptor (21).…”

mentioning

confidence: 99%

Maternal Caffeine Intake Has Minor Effects on Adenosine Receptor Ontogeny in the Rat Brain

Ådén

Herlenius²,

Tang³

et al. 2000

Pediatr Res

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confidence: 99%

Maternal Caffeine Intake Has Minor Effects on Adenosine Receptor Ontogeny in the Rat Brain

Ådén

Herlenius²,

Tang³

et al. 2000

Pediatr Res

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“…Caffeine exerts multiple effects at the cellular level on the central nervous system (CNS); for instance, antagonizes adenosine receptor (2), inhibits GABA receptor-mediated effect (3), and inhibits phosphodiesterase (4). In electrophysiological studies, caffeine at high concentrations triggered Ca 2+ release via ryanodine receptors (5,6), and it is known as a classic pharmacological agonist for activating Ca 2+ -induced Ca 2+ release.…”

Section: Introductionmentioning

confidence: 99%

Caffeine Induces Apoptosis in Human Neuroblastoma Cell Line SK-N-MC

et al. 2002

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Caffeine is one of the most widely consumed neuroactive drugs, coming mostly from everyday beverages such as coffee and tea. To investigate whether caffeine induces apoptosis in the central nervous system, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, 4,6-diamidino-2-phenylindole (DAPI) staining, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay, flow cytometric analysis, DNA fragmentation assay, and caspase-3 enzyme assay were performed on SK-N-MC human neuroblastoma cells. Cells treated with caffeine at concentrations as high as 10 mM exhibited several characteristics of apoptosis. In addition, caffeine was shown to increase the caspase-3 activity. These results suggest that high-dose of caffeine induces apoptosis in human neuroblastoma cells, probably by increasing the caspase-3 enzyme activity.

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“…To date, there have been some reports of the inhibitory effect of methylxanthines on GABA-benzodiazepine receptors (Izquierdo, 1986;Lopez et al, 1989), but there has been no report concerning the effect on glycine receptors.…”

Section: Discussionmentioning

confidence: 99%

“…The half-maximum inhibitory concentrations (IC50) of caffeine on 10-4 M glycine-and 10-5M GABAinduced responses were 4.5 x 10-4 and 3.6 x 10-3 M, respectively ( Figure 2b). The following experiments were confined to the inhibitory action of caffeine on the glycine response since the antagonistic effects of caffeine on GABA responses has been described previously (Izquierdo, 1986;Lopez et al, 1989).…”

Section: Resultsmentioning

confidence: 99%

“…However, the molecular mechanisms for the CNS stimulant effects of caffeine are unclear, because caffeine has multiple actions at the cellular level. For instance, caffeine antagonizes adenosine (Day et al, 1991) and GABA receptor-mediated effects (Izquierdo, 1986;Lopez et al, 1989), inhibits phosphodiesterase (Butcher & Sutherland, 1962), and stimulates Ca2" release from the endoplasmic reticulum (Endo et al, 1970).…”

Section: Introductionmentioning

confidence: 99%

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Caffeine and related compounds block inhibitory amino acid‐gated Cl⁻ currents in freshly dissociated rat hippocampal neurones

Uneyama

Harata

Akaike

1993

British J Pharmacology

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1 The effects of caffeine and related compounds on responses mediated by inhibitory amino acids were investigated in freshly dissociated rat hippocampal pyramidal neurones by conventional and nystatin perforated patch-clamp techniques. 2 Glycine and y-aminobutyric acid (GABA) evoked Cl-currents in hippocampal neurones. The half-maximum effective concentrations (EC_O) of glycine and GABA were 8.5 x 10-5 and 5 x 10-6 M, respectively. 3 Caffeine reversibly inhibited both 10-4M glycine-and 10-M GABA-induced Cl-currents in a concentration-dependent manner. The half-maximum inhibitory concentrations (IC5o) of caffeine were 4.5 x 10-4 M for the glycine response and 3.6 x 10-3 M for the GABA response. 4 Caffeine shifted the concentration-response curve of IGIy to the right without affecting the maximum response. 5 The inhibitory action of caffeine did not show voltage-dependency.6 The blocking action of caffeine was not affected by intracellular perfusion with 5 mM BAPTA or by pretreatment with the protein kinase A inhibitor, H-8. This excludes the participation of Ca2" or cyclic AMP in the inhibitory action of caffeine. 7 Caffeine failed to inhibit the augmentations of aspartate-and N-methyl-D-aspartate (NMDA) -gated current by glycine, suggesting that caffeine has no effect on the allosteric glycine binding site on the NMDA receptor.8 The inhibitory effects of some xanthine derivatives on IGIy were compared. The inhibitory potency of those compounds on IG1y was in the order of pentoxifylline > theophylline > caffeine > paraxanthine > IBMX > theobromine > dyphylline. Xanthine had no effect. 9 The results indicate that methylxanthines including caffeine may act directly on the glycine receptor Cl-channel complex in rat hippocampal pyramidal neurones. The blockade of the inhibitory amino acid response by methylxanthines may be involved in the excitatory side effects of methylxanthines in the mammalian central nervous system.

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Interaction of caffeine with the GABAA receptor complex: alterations in receptor function but not ligand binding

Cited by 50 publications

References 21 publications

Maternal Caffeine Intake Has Minor Effects on Adenosine Receptor Ontogeny in the Rat Brain

Maternal Caffeine Intake Has Minor Effects on Adenosine Receptor Ontogeny in the Rat Brain

Caffeine Induces Apoptosis in Human Neuroblastoma Cell Line SK-N-MC

Caffeine and related compounds block inhibitory amino acid‐gated Cl⁻ currents in freshly dissociated rat hippocampal neurones

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Interaction of caffeine with the GABAA receptor complex: alterations in receptor function but not ligand binding

Cited by 50 publications

References 21 publications

Maternal Caffeine Intake Has Minor Effects on Adenosine Receptor Ontogeny in the Rat Brain

Maternal Caffeine Intake Has Minor Effects on Adenosine Receptor Ontogeny in the Rat Brain

Caffeine Induces Apoptosis in Human Neuroblastoma Cell Line SK-N-MC

Caffeine and related compounds block inhibitory amino acid‐gated Cl− currents in freshly dissociated rat hippocampal neurones

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Caffeine and related compounds block inhibitory amino acid‐gated Cl⁻ currents in freshly dissociated rat hippocampal neurones