Köfalvi Attila, Oliveira Catarina R, Cunha Rodrigo A
Center for Neurosciences of Coimbra, Institute of Biochemistry, Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal.
Neurosci Lett. 2006 Jul 31;403(1-2):151-6. doi: 10.1016/j.neulet.2006.04.030. Epub 2006 May 2.
Although TRPV(1) vanilloid receptors (TRPV(1)Rs) have been assumed to be present in the brain, their role is not well-defined. Here, we tested the widely used TRPV(1)R agonists (E)-capsaicin (0.1-100 microM) and resiniferatoxin (RTX, 0.1 microM) on resting and K(+)-evoked Ca(2+) entry and radiolabelled GABA release in rat hippocampal nerve terminals. (E)-capsaicin and RTX failed to evoke Ca(2+) transients or to trigger [(3)H]GABA outflow. Both (E)-capsaicin (EC(50), 40.4 microM) and its enantiomer (Z)-capsaicin (EC(50), 22.9 microM), which is inactive at the TRPV(1)R, inhibited the K(+)-evoked Ca(2+) entry, and to similar extent, the Ca(2+)-dependent K(+)-evoked [(3)H]GABA release. The TRPV(1)R enhancer/partial agonist 2-aminoethoxydiphenyl borate (1-300 microM) induced rapid Ca(2+) entry. None of the above-mentioned findings proved to be sensitive to the TRPV(1)R antagonists iodoresiniferatoxin (I-RTX; 3 microM) and SB366791 (3 microM). The CB(1) cannabinoid receptor antagonist AM251 (EC(50), 1.1 microM) and I-RTX (EC(50), 4.6 microM) also diminished the K(+)-evoked Ca(2+) entry per se. We observed competitive antagonism between I-RTX and AM251, indicating that the two molecules may act at the same site. In conclusion, there is a need to examine the discrepancy between ex vivo and in vitro data to understand the neurochemical and physiological functions of brain TRPV(1)Rs.
尽管人们认为瞬时受体电位香草酸亚型1（TRPV(1)）香草酸受体（TRPV(1)Rs）存在于大脑中，但其作用尚未明确界定。在此，我们在大鼠海马神经末梢检测了广泛使用的TRPV(1)R激动剂（E）-辣椒素（0.1 - 100微摩尔）和树脂毒素（RTX，0.1微摩尔）对静息和钾离子诱发的钙离子内流以及放射性标记的γ-氨基丁酸（GABA）释放的影响。（E）-辣椒素和RTX未能诱发钙离子瞬变或触发[³H]GABA外流。（E）-辣椒素（半数有效浓度[EC(50)]，40.4微摩尔）及其对映体（Z）-辣椒素（EC(50)，22.9微摩尔，在TRPV(1)R上无活性）均抑制钾离子诱发的钙离子内流，且在相似程度上抑制钙离子依赖性钾离子诱发的[³H]GABA释放。TRPV(1)R增强剂/部分激动剂2-氨基乙氧基二苯硼酸（1 - 300微摩尔）诱导快速钙离子内流。上述发现均未被证明对TRPV(1)R拮抗剂碘树脂毒素（I-RTX；3微摩尔）和SB366791（3微摩尔）敏感。大麻素1型（CB(1)）大麻素受体拮抗剂AM251（EC(50)，1.1微摩尔）和I-RTX（EC(50)，4.6微摩尔）本身也减少了钾离子诱发的钙离子内流。我们观察到I-RTX和AM251之间存在竞争性拮抗作用，表明这两种分子可能作用于同一部位。总之，有必要研究体外和体内数据之间的差异，以了解大脑TRPV(1)Rs的神经化学和生理功能。
