Praziquantel leads to increase Ca²⁺ influx and disrupts Ca²⁺ homeostasis in adult Schistosoma. However, calcium influx is only one component in a series of molecular events leading to the drug effect and some downstream constituents of the cascade that is initiated by this interaction differ between worms with different degrees of susceptibility to praziquantel. Extensive use of the drug raises the concern regarding the selection of drug resistant parasites. SERCA participates in maintenance of Ca²⁺ homeostasis. Up-regulation of SERCA has been found in Schistosoma mansoni worms with reduced sensitivity to praziquantel. This could be due to increase cytosolic Ca²⁺, activation of calmodulin kinase II or may be due to SR/ER stress generated from oxidative stress that leads to impaired protein degradation. The significance of SERCA up-regulation is related to counter action of the drug effect by increasing the worm capacity to restore Ca²⁺ homeostasis, reducing cytosolic Ca²⁺ followed by lowering mitochondria Ca²⁺ and consequently inhibition of apoptosis beside its relation to P-glycoprotein. In schistosomes with reduced sensitivity to praziquantel, the agitations produced by Ca²⁺ influx and the downstream component of the cascade that is initiated by this interaction may be opposed by up-regulation of SERCA and possibly by certain elements of Ca²⁺ signaling which modulate the process determining cells entrance in the apoptotic state. Revealing the principal mechanisms of up-regulation of SERCA and its significance in reducing the effect of the drug could lead to possible strategies to reverse drug resistance or develop alternative therapies.

吡喹酮导致增加的Ca ²⁺内流，破坏钙²⁺动态平衡成人血吸虫。但是，钙流入只是一系列导致药物作用的分子事件中的一个组成部分，由这种相互作用引发的级联反应的一些下游成分在对吡喹酮有不同程度敏感性的蠕虫之间有所不同。药物的广泛使用引起了对耐药性寄生虫的选择的关注。SERCA参与Ca ²⁺稳态的维持。在曼氏血吸虫蠕虫中发现了SERCA的上调，对吡喹酮的敏感性降低。这可能是由于胞质Ca ²⁺增加，钙调蛋白激酶II的激活或可能是由于氧化应激产生的SR / ER应激导致蛋白质降解受损。SERCA上调的意义与药物作用的反作用有关，该作用是通过提高蠕虫恢复Ca ²⁺稳态的能力，降低胞质Ca ^{2+的含量，}然后降低线粒体Ca ^{2+的含量，}进而抑制细胞凋亡来实现的。 -糖蛋白。在对吡喹酮敏感性降低的血吸虫中，Ca ^2+内流和级联反应的下游成分（由这种相互作用引发）产生的搅动可能与SERCA的上调（可能与Ca ^2+的某些元素）相反信号调节细胞凋亡过程中决定细胞进入的过程。揭示SERCA上调的主要机制及其在降低药物作用中的意义可能会导致逆转耐药性或开发替代疗法的可能策略。