Bruno Alessandra Nejar, Fontella Fernanda Urruth, Crema Leonardo Machado, Bonan Carla Denise, Dalmaz Carla, Barreto-Chaves Maria Luiza M, Sarkis João José Freitas
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Avenida Ramiro Barcellos 2600-ANEXO, 90035-003, Porto Alegre, RS, Brazil.
Comp Biochem Physiol A Mol Integr Physiol. 2005 Jan;140(1):111-6. doi: 10.1016/j.cbpb.2004.11.007.
Changes in transport, receptors and production of extracellular adenosine have been observed after induction of hyperthyroidism. Adenosine is associated with inhibitory actions such as reduction in release of excitatory neurotransmitters and antinociception at spinal site. In contrast, ATP acts as an excitatory neurotransmitter and produces pronociceptive actions. ATP may be completely hydrolyzed to adenosine by an enzyme chain constituted by an ATP diphosphohydrolase and an ecto-5'-nucleotidase, as previously described in the spinal cord. Thus, we now investigated the effects of the hyperthyroidism on adenine nucleotide hydrolysis in the spinal cord and verified the nociceptive response in this pathology during different phases of development. Hyperthyroidism was induced in male Wistar rats, aged 5, 60 and 330 days by daily intraperitoneal injections of L-thyroxine (T4) for 14 days. Nociception was assessed with a tail-flick apparatus. Rats starting the treatment aged 5 days demonstrated a significant increase in ADP and AMP hydrolysis and increased tail-flick latency (TFL). In contrast, in the spinal cord from hyperthyroid rats aged 60 and 330 days old, the hydrolysis of ATP, ADP and AMP were significantly decreased. Accordingly, the tail-flick latency was decreased, indicating a hyperalgesic response. These results suggest the involvement of ecto-nucleotidases in the control of the hyperthyroidism-induced nociceptive response in rats at distinct developmental stages.
甲状腺功能亢进诱导后，已观察到细胞外腺苷的转运、受体及生成的变化。腺苷与抑制性作用相关，如减少兴奋性神经递质的释放及在脊髓部位的抗伤害感受作用。相反，ATP作为一种兴奋性神经递质，产生促伤害感受作用。如先前在脊髓中所描述，ATP可被由ATP二磷酸水解酶和胞外5'-核苷酸酶构成的酶链完全水解为腺苷。因此，我们现在研究了甲状腺功能亢进对脊髓中腺嘌呤核苷酸水解的影响，并验证了在该病理状态不同发育阶段的伤害性反应。通过每日腹腔注射L-甲状腺素（T4）持续14天，诱导5日龄、60日龄和330日龄雄性Wistar大鼠发生甲状腺功能亢进。用甩尾装置评估伤害感受。开始治疗时5日龄的大鼠表现出ADP和AMP水解显著增加，甩尾潜伏期（TFL）延长。相反，在60日龄和330日龄甲状腺功能亢进大鼠的脊髓中，ATP、ADP和AMP的水解显著减少。相应地，甩尾潜伏期缩短，表明存在痛觉过敏反应。这些结果提示胞外核苷酸酶参与了不同发育阶段大鼠甲状腺功能亢进诱导的伤害性反应的调控。
