Sapru H N, Willette R N, Krieger A J
J Pharmacol Exp Ther. 1981 Apr;217(1):228-34.
Respiratory and cardiovascular actions of a stable enkephalin-analog (EA), D-met2-pro5-enkephalinamide, were studied in decerebrate male Wistar rats. Injection of a small dose of EA (10 micrograms/kg) into the right atrium produced apnea, bradycardia and hypotension within 1 to 2 sec. These effects lasted for 2 to 4 sec. Apnea was followed by a period of fast and shallow breathing which lasted for 7 to 10 min. The decrease in heart rate and mean blood pressure was 26 +/- 3% (S.E.) and 12 +/- 1.5% (S.E.), respectively. Higher doses of EA used in this study (100,500 and 1,000 micrograms/kg, right atrium) produced similar responses. However, the durations of apnea and fst and shallow breathing and magnitudes of bradycardia and hypotension were greater with the higher doses. Bilateral vagotomy (low in the neck) abolished these effects. These actions are typical of pulmonary J receptor stimulation. Nerve recording experiments in artificially ventilated rats showed that interruption of vagal innervation to the lungs abolished the EA-induced cessation of phrenic nerve activity (apnea), increased frequency of phrenic nerve bursts (fast breathing) and decreased spike activity in each burst (shallow breathing). These results suggested that EA stimulated lung sensory receptors. Of the known lung sensory receptors (stretch, irritant and J. receptors), only pulmonary J receptors are known to produce apnea, bradycardia and hypotension. Direct recordings from pulmonary J receptor fibers in thin filaments of vagus confirmed that EA stimulates these receptors.
在去大脑的雄性Wistar大鼠中研究了一种稳定的脑啡肽类似物（EA），即D-蛋氨酸²-脯氨酸⁵-脑啡肽酰胺的呼吸和心血管作用。向右心房注射小剂量的EA（10微克/千克）会在1至2秒内产生呼吸暂停、心动过缓和低血压。这些效应持续2至4秒。呼吸暂停之后是一段快速浅呼吸期，持续7至10分钟。心率和平均血压的下降分别为26±3%（标准误）和12±1.5%（标准误）。本研究中使用的较高剂量的EA（100、500和1000微克/千克，右心房）产生了类似的反应。然而，较高剂量时呼吸暂停、快速浅呼吸的持续时间以及心动过缓和低血压的程度更大。双侧迷走神经切断术（在颈部低位）消除了这些效应。这些作用是肺J受体刺激的典型表现。在人工通气的大鼠中进行的神经记录实验表明，切断迷走神经对肺的支配消除了EA诱导的膈神经活动停止（呼吸暂停）、增加了膈神经冲动频率（快速呼吸）并降低了每个冲动中的锋电位活动（浅呼吸）。这些结果表明EA刺激了肺感觉受体。在已知的肺感觉受体（牵张、刺激和J受体）中，只有肺J受体已知会产生呼吸暂停、心动过缓和低血压。从迷走神经细丝中的肺J受体纤维进行的直接记录证实EA刺激了这些受体。
