Kaczyńska Katarzyna, Wojciechowski Piotr, Jampolska Monika, Lipkowski Andrzej W, Kleczkowska Patrycja
Laboratory of Respiration Physiology, Mossakowski Medical Research Centre Polish Academy of Sciences, Warsaw, Poland.
Laboratory of Respiration Physiology, Mossakowski Medical Research Centre Polish Academy of Sciences, Warsaw, Poland.
Eur J Pharmacol. 2017 Feb 15;797:20-25. doi: 10.1016/j.ejphar.2017.01.010. Epub 2017 Jan 12.
Chimeric compound - PK20 despite its therapeutic activity on nociceptive and inflammatory processes may affect respiration and blood pressure. Our objective was to evaluate influence of the hybrid composed of endomorphin-2 and neurotensin fragments on ventilation, heart rate and blood pressure in anesthetized and awake rats.
The effects of PK20 (1mg/kg) were studied either after its intravenous administration in anesthetized rats or intraperitoneal injection in awake state. Tidal volume and the timing components of the breathing pattern, arterial blood pressure, and heart rate were recorded.
Intravenous administration of PK20 in the neurally intact rats evoked a dose-dependent apnoea followed by a transient insignificant increase in tidal volume and breathing rate. The blood pressure changes were biphasic: transient increase was replaced by prolonged hypotension. Midcervical vagotomy abrogated all post-PK20 respiratory effects. Hypotension was eliminated after blockade of neurotensin NTS receptor, while respiratory changes were reduced by blockade of both: NTS and μ opioid receptors. After PK20 intraperitoneal injection awake rats did not show any significant changes in ventilation and blood pressure.
This chimeric peptide should be used with care via intravenous administration in anesthetized animals since PK20 may evoke respiratory apnoea and hypotension. Nevertheless, applied intraperitoneally in the same dose in conscious rats induced no adverse effects.
嵌合化合物PK20尽管对伤害性和炎症过程具有治疗活性，但可能会影响呼吸和血压。我们的目的是评估由内吗啡肽-2和神经降压素片段组成的杂合体对麻醉和清醒大鼠的通气、心率和血压的影响。
研究了PK20（1mg/kg）在麻醉大鼠静脉注射或清醒状态下腹腔注射后的作用。记录潮气量、呼吸模式的时间成分、动脉血压和心率。
在神经完整的大鼠中静脉注射PK20会引起剂量依赖性呼吸暂停，随后潮气量和呼吸频率短暂出现无显著意义的增加。血压变化呈双相性：短暂升高后被持续性低血压所取代。颈中部迷走神经切断术消除了PK20后的所有呼吸效应。神经降压素NTS受体阻断后低血压消失，而NTS和μ阿片受体两者阻断后呼吸变化减轻。PK20腹腔注射后，清醒大鼠的通气和血压未出现任何显著变化。
在麻醉动物中通过静脉给药时应谨慎使用这种嵌合肽，因为PK20可能会引起呼吸暂停和低血压。然而，以相同剂量腹腔注射给清醒大鼠则不会产生不良反应。
