Abstract：
BACKGROUND: Dimenhydrinate and scopolamine are frequently used drugs, but they cause drowsiness and performance decrement. Therefore, it is crucial to find peripheral targets and develop new drugs without central side effects. This study aimed to investigate the anti-motion sickness action and inner ear-related mechanisms of atrial natriuretic peptide (ANP).
METHODS: Endolymph volume in the inner ear was measured with magnetic resonance imaging and expression of AQP2 and p-AQP2 was detected with Western blot analysis and immunofluorescence method.
RESULTS: Both rotational stimulus and intraperitoneal arginine vasopressin (AVP) injection induced conditioned taste aversion (CTA) to 0.15% sodium saccharin solution and an increase in the endolymph volume of the inner ear. However, intraperitoneal injection of ANP effectively alleviated the CTA behaviour and reduced the increase in the endolymph volume after rotational stimulus. Intratympanic injection of ANP also inhibited rotational stimulus-induced CTA behaviour, but anantin peptide, an inhibitor of ANP receptor A (NPR-A), blocked this inhibitory effect of ANP. Both rotational stimulus and intraperitoneal AVP injection increased the expression of AQP2 and p-AQP2 in the inner ear of rats, but these increases were blunted by ANP injection. In in vitro experiments, ANP addition decreased AVP-induced increases in the expression and phosphorylation of AQP2 in cultured endolymphatic sac epithelial cells.
CONCLUSIONS: Therefore, the present study suggests that ANP could alleviate motion sickness through regulating endolymph volume of the inner ear increased by AVP, and this action of ANP is potentially mediated by activating NPR-A and antagonising the increasing effect of AVP on AQP2 expression and phosphorylation.
METHODS: Endolymph volume in the inner ear was measured with magnetic resonance imaging and expression of AQP2 and p-AQP2 was detected with Western blot analysis and immunofluorescence method.
RESULTS: Both rotational stimulus and intraperitoneal arginine vasopressin (AVP) injection induced conditioned taste aversion (CTA) to 0.15% sodium saccharin solution and an increase in the endolymph volume of the inner ear. However, intraperitoneal injection of ANP effectively alleviated the CTA behaviour and reduced the increase in the endolymph volume after rotational stimulus. Intratympanic injection of ANP also inhibited rotational stimulus-induced CTA behaviour, but anantin peptide, an inhibitor of ANP receptor A (NPR-A), blocked this inhibitory effect of ANP. Both rotational stimulus and intraperitoneal AVP injection increased the expression of AQP2 and p-AQP2 in the inner ear of rats, but these increases were blunted by ANP injection. In in vitro experiments, ANP addition decreased AVP-induced increases in the expression and phosphorylation of AQP2 in cultured endolymphatic sac epithelial cells.
CONCLUSIONS: Therefore, the present study suggests that ANP could alleviate motion sickness through regulating endolymph volume of the inner ear increased by AVP, and this action of ANP is potentially mediated by activating NPR-A and antagonising the increasing effect of AVP on AQP2 expression and phosphorylation.
摘要：
背景：苯海尼酯和东pol碱是经常使用的药物，但它们会导致嗜睡和表现下降。因此,寻找外周靶点和开发无中枢副作用的新药至关重要。本研究旨在探讨ANP的抗晕动病作用及内耳相关机制。
方法：用磁共振成像测量内耳内淋巴体积，用Westernblot分析和免疫荧光法检测AQP2和p-AQP2的表达。
结果：旋转刺激和腹膜内注射AVP均可诱导对0.15％糖精钠溶液的条件厌恶（CTA）和内耳内淋巴体积的增加。然而,腹腔注射ANP可有效缓解CTA行为,并减少旋转刺激后内淋巴体积的增加。鼓室内注射ANP也抑制了旋转刺激诱导的CTA行为，但是Anantin肽,ANP受体A（NPR-A）的抑制剂，阻断了ANP的这种抑制作用。旋转刺激和腹腔注射AVP均可增加大鼠内耳AQP2和p-AQP2的表达,但是这些增加被ANP注射所抑制。在体外实验中,添加ANP降低了AVP诱导的培养内淋巴囊上皮细胞中AQP2表达和磷酸化的增加。
结论：因此，本研究表明，ANP可以通过调节AVP增加的内耳内淋巴容量来缓解晕动病，ANP的这种作用可能通过激活NPR-A和拮抗AVP对AQP2表达和磷酸化的增加作用来介导。
方法：用磁共振成像测量内耳内淋巴体积，用Westernblot分析和免疫荧光法检测AQP2和p-AQP2的表达。
结果：旋转刺激和腹膜内注射AVP均可诱导对0.15％糖精钠溶液的条件厌恶（CTA）和内耳内淋巴体积的增加。然而,腹腔注射ANP可有效缓解CTA行为,并减少旋转刺激后内淋巴体积的增加。鼓室内注射ANP也抑制了旋转刺激诱导的CTA行为，但是Anantin肽,ANP受体A（NPR-A）的抑制剂，阻断了ANP的这种抑制作用。旋转刺激和腹腔注射AVP均可增加大鼠内耳AQP2和p-AQP2的表达,但是这些增加被ANP注射所抑制。在体外实验中,添加ANP降低了AVP诱导的培养内淋巴囊上皮细胞中AQP2表达和磷酸化的增加。
结论：因此，本研究表明，ANP可以通过调节AVP增加的内耳内淋巴容量来缓解晕动病，ANP的这种作用可能通过激活NPR-A和拮抗AVP对AQP2表达和磷酸化的增加作用来介导。
