Jackson K E, Farias M, Stanfill A, Caffrey J L
Department of Integrative Physiology and Cardiovascular Research Institute, University of North Texas Health Science Center in Fort Worth, Fort Worth, Texas 76107, USA.
J Cardiovasc Pharmacol Ther. 2001 Oct;6(4):385-93. doi: 10.1177/107424840100600408.
Methionine-enkephalin-arginine-phenylalanine (MEAP) is an endogenous opiate derived from the C-terminal sequence of the larger precursor molecule proenkephalin. This heptapeptide is abundant in the myocardium and has significant vagolytic activity when infused systemically. MEAP interrupted vagal bradycardia when it was delivered directly into the sinoatrial node by local microdialysis. This study was conducted to determine the opioid receptor responsible for the vagolytic effect of MEAP.
Microdialysis probes were placed in the sinoatrial node of mongrel dogs and perfused at 5 microL/min. Increasing doses of MEAP were included in the nodal perfusate and approximately two thirds of the vagal bradycardia was inhibited with a maximal effect at 0.3 nmoles/microL and a half-maximal response near 0.1 nmoles/microL. When deltorphin II (a delta opioid receptor agonist) was infused into the sinoatrial node, more than 95% of the vagal bradycardia was eliminated at 0.3 nmoles/microL with the half-maximal response near 0.1 nmoles/microL, indicating that deltorphin II was more efficacious than MEAP. The maximal deltorphin II and MEAP effects were both similarly reversed by the paired infusion of increasing doses of the delta opiate receptor antagonist, naltrindole. Selected mu (endomorphin, super DALDA) and kappa (dynorphin, U50488) receptor agonists and mu (CTAP) and kappa (norBNI) receptor antagonists were completely ineffective in this system.
These data suggest that the vagolytic effect of MEAP involves the activation of delta opiate receptors within the sinoatrial node.
甲硫氨酸脑啡肽 - 精氨酸 - 苯丙氨酸（MEAP）是一种内源性阿片肽，源自较大前体分子前脑啡肽的C末端序列。这种七肽在心肌中含量丰富，全身输注时具有显著的抗迷走神经活性。通过局部微透析将MEAP直接注入窦房结时，可中断迷走神经性心动过缓。本研究旨在确定介导MEAP迷走神经溶解作用的阿片受体。
将微透析探针置于杂种犬的窦房结中，以5微升/分钟的速度灌注。在节点灌注液中加入递增剂量的MEAP，约三分之二的迷走神经性心动过缓受到抑制，最大效应出现在0.3纳摩尔/微升，半最大反应接近0.1纳摩尔/微升。当将德尔托啡肽II（一种δ阿片受体激动剂）注入窦房结时，在0.3纳摩尔/微升时超过95%的迷走神经性心动过缓被消除，半最大反应接近0.1纳摩尔/微升，表明德尔托啡肽II比MEAP更有效。递增剂量的δ阿片受体拮抗剂纳曲吲哚配对输注可同样逆转德尔托啡肽II和MEAP的最大效应。选定的μ（内吗啡肽、超级DALDA）和κ（强啡肽、U50488）受体激动剂以及μ（CTAP）和κ（norBNI）受体拮抗剂在该系统中完全无效。
这些数据表明，MEAP的迷走神经溶解作用涉及窦房结内δ阿片受体的激活。
