ENKEPHALIN, A MYOCARDIAL HORMONE

心脏通过释放来主动协调心血管反应 荷尔蒙的作用。脑室前脑啡肽信使核糖核酸含量是 大脑提示脑啡肽起心脏激素的作用。我们发现 脑啡肽在狗的心脏中均匀分布，但前脑啡肽 脑室比心房高3-5倍，前脑啡肽含量是 比脑啡肽高10倍。这与去甲肾上腺素不同，去甲肾上腺素 集中在心房，表明脑啡肽不储存在 心脏神经。我们还描述了脑室的免疫荧光 脑啡肽原抗体染色的组织。荧光图案 描述了心肌细胞内的前脑啡肽原，并与 与脑室神经支配相关的模式。 心肌脑啡肽在出血后急剧下降，并 去神经支配和神经节阻滞后增加。此外, 反复刺激节后心脏神经可导致 去甲肾上腺素冠脉溢出量的阿片依赖下降。 总之，这些观察表明，神经元的传递 随着阿片类药物的释放，在心脏内启动阿片类药物反馈循环 自主神经激活过程中的阿片类药物及其蓄积 神经节阻滞症。我们认为心脏阿片类药物是重要的调节剂 心肌兴奋性。过量的阿片类药物可能会导致心脏 休克时观察到的抑郁；相反，阿片类药物不足可能 导致易怒情绪增加，导致心律失常。我们的结果 证明心肌脑啡肽对自主神经的改变有反应 功能，这导致了我们的假设，自主神经输入心脏 调节心脏脑啡肽的合成和分泌。 我们建议收集有控制、减少和减少的动物的心脏 增强自主神经活动以：a)表征脑啡肽分泌： 心脏组织将被灌流以评估其含量和分泌 脑啡肽和前脑啡肽对电、离子和电刺激的反应 激素刺激；B)提取和鉴定心脏脑啡肽和 脑啡肽原信使核糖核酸：将从心脏组织中提取脑啡肽 并经层析鉴定，注意其相对含量 前体VS产品。前脑啡肽mRNA将通过以下方法定量 Northern印迹分析。C)脑啡肽的解剖学定位：心脏 组织将准备用于免疫组织化学使用免疫金 脑啡肽原和脑啡肽的识别技术和抗体。 总而言之，这些研究应该提供有关这一角色的重要信息 阿片类药物及其对心脏功能的自主神经调节。

The heart actively coordinates cardiovascular responses through release of hormones. Ventricular proenkephalin mRNA content is twice that of brain suggesting that enkephalins function as cardiac hormones. We find enkephalins evenly distributed throughout dog heart, but proenkephalin is 3-5 X higher in ventricles than in atria and proenkephalin content is 10 X higher than enkephalin. This differs from norepinephrine which is concentrated in the atria and suggests that enkephalin is not stored in cardiac nerves. We also describe immunofluorescence in ventricular tissue stained with a proenkephalin antibody. The fluorescent pattern depicts proenkephalin within myocytes and was clearly distinct from patterns associated with ventricular innervation. Myocardial enkephalins declined sharply following hemorrhage and increased after denervation and ganglionic blockade. In addition, repeated stimulation of the post ganglionic cardiac nerve leads to an opioid dependent decline in coronary overflow of norepinephrine. Together, these observations indicate that neuronal transmission initiates an opioid feedback loop within the heart with the release of opioids during autonomic activation and their accumulation following ganglionic blockade. We believe cardiac opioids are important governors of myocardial excitability. Excess opioids might contribute to cardiac depression as observed in shock; conversely, insufficient opioids may lead to increasing irritability causing arrhythmias. Our results demonstrate myocardial enkephalins respond to alterations in autonomic function which leads to our hypothesis that autonomic input to the heart regulates synthesis and secretion of cardiac enkephalins. We propose to collect hearts from animals with control, diminished and augmented autonomic activity to: A) Characterize Enkephalin Secretion: Cardiac tissue will be perfused to evaluate the content and secretion of enkephalin and proenkephalin in response to electrical, ionic and hormonal stimuli; B) Extract and Identify Cardiac Enkephalins and Proenkephalin mRNA: Enkephalins will be extracted from cardiac tissue and chromatographically identified with attention to relative content of precursors vs products. Proenkephalin mRNA will be quantitated by Northern blot analysis. C) Localize Enkephalins Anatomically: Cardiac tissue will be prepared for immunohistochemistry utilizing immunogold techniques and antibodies recognizing proenkephalin and enkephalin. Together, these studies should provide important information on the role of opioids and their autonomic regulation in heart function.