Araujo F P, Quintas L E M, Noël F, Silva C L M
Departamento de Farmacologia Básica & Clínica, Universidade Federal do Rio de Janeiro, CCS, sl. J01-17, Cidade Universitária, Rio de Janeiro, RJ 21941-590, Brazil.
Microbes Infect. 2007 Jul;9(8):1020-5. doi: 10.1016/j.micinf.2007.04.007. Epub 2007 Apr 21.
Murine Schistosoma mansoni infection is related to an increased contraction of portal vein in response to 5-hydroxytryptamine (5-HT). The present study addressed a putative alteration of ion channels and enzymes involved in vascular contraction. In control group, either inhibition of K+ channels sensitive to ATP (K(ATP)) or Ca2+ (BK(Ca)) increased 5-HT-induced contraction, but the same did not occur in infected mice. On the other hand, inhibition of p38 MAP kinase markedly decreased the vascular contraction to 5-HT in the infected mice with minor effects in the control group. Accordingly, we observed a higher density of phospho-p38 MAP kinase, that refers to the fully active state of the enzyme, in portal veins from infected mice as compared to control animals. These results suggest that the reduced function of K(ATP) and BK(Ca) channels along with an increased contribution of p38 MAP kinase contribute to the increased contraction of portal veins to 5-HT observed in murine schistosomiasis.
小鼠曼氏血吸虫感染与门静脉对5-羟色胺(5-HT)反应性收缩增强有关。本研究探讨了参与血管收缩的离子通道和酶的假定改变。在对照组中,抑制对ATP敏感的K+通道(K(ATP))或Ca2+通道(BK(Ca))会增加5-HT诱导的收缩,但在感染小鼠中未出现同样情况。另一方面,抑制p38丝裂原活化蛋白激酶(p38 MAP激酶)可显著降低感染小鼠对5-HT的血管收缩,而对对照组影响较小。相应地,我们观察到与对照动物相比,感染小鼠门静脉中磷酸化p38 MAP激酶(指该酶的完全活性状态)的密度更高。这些结果表明,K(ATP)和BK(Ca)通道功能降低以及p38 MAP激酶作用增强,导致了在小鼠血吸虫病中观察到的门静脉对5-HT收缩增强。