Department of Clinical Physiology, Faculty of Veterinary Medicine, University of Warmia and Mazury, Oczapowskiego 13, 10-718 Olsztyn, Poland.
Institute of Animal Reproduction and Food Research of the Polish Academy of Sciences, Tuwima 10, 10-748 Olsztyn, Poland.
Int J Mol Sci. 2022 Oct 29;23(21):13184. doi: 10.3390/ijms232113184.
Disturbances in uterine contractile activity contribute to the development of inflammation, and recent evidence indicates that tachykinins, including substance P (SP) and neurokinin A (NKA), are involved in controlling uterine function. Here, we determined the effect of (-induced inflammation on expression of protein receptor subtypes for substance P (NK1R) and neurokinin A (NK2R) in the pig myometrium as well as their role in contractility of inflamed uterus. The severe acute endometritis developed in the group and the expression of NK1R and NK2R proteins increased in the myometrium. Compared to the pre-administration period, SP (10 M) reduced the amplitude and frequency in the myometrium of the group and the amplitude was higher and the frequency was lower versus other groups. NKA reduced the amplitude and increased the frequency in endometrium/myometrium of the group. In this group, the amplitude was lower and the frequency was higher than in the CON and SAL groups. Our research showed that NK2R (10 M) antagonist application abolished the NKA inhibitory effect on uterine amplitude. The application of the NK1R (10 M) antagonist together with SP revealed that the inhibitory effect of SP on uterine contractility is achieved independently of the NKR1. Additionally, taking into account the fact that NKA shows an inhibitory effect with the use of NK2R on uterine amplitude suggests the possibility of therapeutic use of the antagonist as a drug increasing uterine contractility in inflammation.
子宫收缩活动的紊乱会导致炎症的发展，最近的证据表明，速激肽（包括 P 物质（SP）和神经激肽 A（NKA））参与控制子宫功能。在这里，我们确定了（-诱导的炎症对猪子宫中 P 物质（NK1R）和神经激肽 A（NK2R）蛋白受体亚型表达的影响，以及它们在炎症子宫收缩中的作用。在组中发生严重急性子宫内膜炎，并且 NK1R 和 NK2R 蛋白的表达在子宫肌层中增加。与给药前时期相比，SP（10M）降低了组中子宫肌层的幅度和频率，并且与其他组相比，幅度更高，频率更低。NKA 降低了组中子宫内膜/子宫肌层的幅度并增加了频率。在该组中，幅度低于 CON 和 SAL 组，频率高于 CON 和 SAL 组。我们的研究表明，NK2R（10M）拮抗剂的应用消除了 NKA 对子宫幅度的抑制作用。NK1R（10M）拮抗剂与 SP 的联合应用表明，SP 对子宫收缩的抑制作用是独立于 NKR1 实现的。此外，考虑到 NKA 与 NK2R 一起使用对子宫幅度具有抑制作用，这表明拮抗剂作为一种增加炎症中子宫收缩力的药物具有治疗用途的可能性。
