Seibt Kelly Juliana, Oliveira Renata da Luz, Rico Eduardo Pacheco, Dias Renato Dutra, Bogo Mauricio Reis, Bonan Carla Denise
Departamento de Biologia Celular e Molecular, Programa de Pós-Graduação em Biologia Celular e Molecular, Faculdade de Biociências, Pontifícia Universidade Católica do Rio Grande do Sul. Avenida Ipiranga, Porto Alegre, RS, Brazil.
Toxicol In Vitro. 2009 Feb;23(1):78-82. doi: 10.1016/j.tiv.2008.10.003. Epub 2008 Nov 1.
Haloperidol (HAL), olanzapine (OLZ), and sulpiride (SULP) are antipsychotic drugs widely used in the pharmacotherapy of psychopathological symptoms observed in schizophrenia or mood-related psychotic symptoms in affective disorders. Here, we tested the in vitro effects of different concentrations of a typical (HAL) and two atypical (OLZ and SULP) antipsychotic drugs on ectonucleotidase activities from zebrafish brain membranes. HAL inhibited ATP (28.9%) and ADP (26.5%) hydrolysis only at 250 microM. OLZ decreased ATPase activity at all concentrations tested (23.8-60.7%). SULP did not promote significant changes on ATP hydrolysis but inhibited ADP hydrolysis at 250 microM (25.6%). All drugs tested, HAL, OLZ, and SULP, did not promote any significant changes on 5'-nucleotidase activity in the brain membranes of zebrafish. These findings demonstrated that antipsychotic drugs could inhibit NTPDase activities whereas did not change 5'-nucleotidase. Such modulation can alter the adenosine levels, since the ectonucleotidase pathway is an important source of extracellular adenosine. Thus, it is possible to suggest that changes promoted by antipsychotic drugs in the bilayer membrane could alter the NTPDase activities, modulating extracellular ATP and adenosine levels.
氟哌啶醇（HAL）、奥氮平（OLZ）和舒必利（SULP）是广泛用于精神分裂症所观察到的精神病理症状或情感障碍中与情绪相关的精神病性症状药物治疗的抗精神病药物。在此，我们测试了不同浓度的一种典型抗精神病药物（HAL）和两种非典型抗精神病药物（OLZ和SULP）对斑马鱼脑膜外核苷酸酶活性的体外影响。HAL仅在250微摩尔浓度时抑制ATP（抑制率28.9%）和ADP（抑制率26.5%）的水解。OLZ在所有测试浓度（23.8 - 60.7%）下均降低了ATP酶活性。SULP对ATP水解未产生显著变化，但在250微摩尔浓度时抑制ADP水解（抑制率25.6%）。所测试的所有药物，HAL、OLZ和SULP，对斑马鱼脑膜中的5'-核苷酸酶活性均未产生任何显著变化。这些发现表明，抗精神病药物可抑制NTPDase活性，而不改变5'-核苷酸酶活性。这种调节可改变腺苷水平，因为外核苷酸酶途径是细胞外腺苷的重要来源。因此，可以推测抗精神病药物在双层膜中所引起的变化可能会改变NTPDase活性，调节细胞外ATP和腺苷水平。
