Caffeine has a dual influence on NMDA receptor–mediated glutamatergic transmission at the hippocampus

Purinergic signalling

article

Robertta S. Martins¹  Diogo M. Rombo¹  Joana Gonçalves-Ribeiro¹  Carlos Meneses⁴  Vladimir P. P. Borges-Martins²  Joaquim A. Ribeiro¹  Sandra H. Vaz¹  Regina C. C. Kubrusly²  Ana M. Sebastião¹ 

[1] Instituto de Farmacologia e Neurociências, Faculdade de Medicina da Universidade de Lisboa;Laboratório de Neurofarmacologia, Departamento de Fisiologia e Farmacologia, Universidade Federal Fluminense;Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina da Universidade de Lisboa;Instituto Superior de Engenharia de Lisboa

关键词: Caffeine;    NMDAR;    Hippocampus;    A1 adenosine receptor;    A2A adenosine receptor;   

DOI  :  10.1007/s11302-020-09724-z

学科分类：分子生物学，细胞生物学和基因

来源: Springer

【 摘 要 】

Caffeine, a stimulant largely consumed around the world, is a non-selective adenosine receptor antagonist, and therefore caffeine actions at synapses usually, but not always, mirror those of adenosine. Importantly, different adenosine receptors with opposing regulatory actions co-exist at synapses. Through both inhibitory and excitatory high-affinity receptors (A1R and A2R, respectively), adenosine affects NMDA receptor (NMDAR) function at the hippocampus, but surprisingly, there is a lack of knowledge on the effects of caffeine upon this ionotropic glutamatergic receptor deeply involved in both positive (plasticity) and negative (excitotoxicity) synaptic actions. We thus aimed to elucidate the effects of caffeine upon NMDAR-mediated excitatory post-synaptic currents (NMDAR-EPSCs), and its implications upon neuronal Ca2+ homeostasis. We found that caffeine (30–200 μM) facilitates NMDAR-EPSCs on pyramidal CA1 neurons from Balbc/ByJ male mice, an action mimicked, as well as occluded, by 1,3-dipropyl-cyclopentylxantine (DPCPX, 50 nM), thus likely mediated by blockade of inhibitory A1Rs. This action of caffeine cannot be attributed to a pre-synaptic facilitation of transmission because caffeine even increased paired-pulse facilitation of NMDA-EPSCs, indicative of an inhibition of neurotransmitter release. Adenosine A2ARs are involved in this likely pre-synaptic action since the effect of caffeine was mimicked by the A2AR antagonist, SCH58261 (50 nM). Furthermore, caffeine increased the frequency of Ca2+ transients in neuronal cell culture, an action mimicked by the A1R antagonist, DPCPX, and prevented by NMDAR blockade with AP5 (50 μM). Altogether, these results show for the first time an influence of caffeine on NMDA receptor activity at the hippocampus, with impact in neuronal Ca2+ homeostasis.

【 授权许可】

CC BY