Farias M, Jackson K, Stanfill A, Caffrey J L
Department of Biology, University of Texas/Brownsville, Brownsville, TX 78520, USA.
Auton Neurosci. 2001 Feb 20;87(1):9-15. doi: 10.1016/S1566-0702(00)00244-7.
Met-enkephalin-arg-phe (MEAP) interrupts vagal bradycardia when infused into the systemic circulation. This study was designed to locate the opiate receptors functionally responsible for this inhibition. Previous observations suggested that the receptors were most likely located in either intracardiac parasympathetic ganglia or the pre-junctional nerve terminals innervating the sinoatrial node. In this study 10 dogs were instrumented with a microdialysis probe inserted into the sinoatrial node. The functional position of the probe was tested by briefly introducing norepinephrine into the probe producing an increase in heart rate of more than 30 beats/min. Vagal stimulations were conducted at 0.5, 1.2 and 4 Hz during vehicle infusion (saline ascorbate). Cardiovascular responses during vagal stimulation were recorded on-line. MEAP was infused directly into the sinoatrial node via the microdialysis probe. The evaluation of vagal bradycardia was repeated during the nodal application of MEAP, diprenorphine (opiate antagonist), and diprenorphine co-infused with MEAP. MEAP introduced into the sinoatrial node via the microdialysis probe reduced vagal bradycardia by more than half. Simultaneous local nodal blockade of these receptors with the opiate antagonist, diprenorphine, eliminated the effect of MEAP demonstrating the participation by opiate receptors. Systemic infusions of MEAP produced a reduction in vagal bradycardia nearly identical to that observed during nodal administration. When local nodal opiate receptors were blocked with diprenorphine, the systemic effect of MEAP was eliminated. These data lead us to suggest that the opiate receptors responsible for the inhibition of vagal bradycardia are located within the sinoatrial node with few, if any, participating extra-nodal or ganglionic receptors.
甲硫氨酸脑啡肽-精氨酸-苯丙氨酸（MEAP）注入体循环时可中断迷走神经介导的心动过缓。本研究旨在定位介导这种抑制作用的阿片受体。先前的观察表明，这些受体很可能位于心内副交感神经节或支配窦房结的节前神经末梢。在本研究中，10只犬通过插入窦房结的微透析探针进行监测。通过向探针中短暂注入去甲肾上腺素使心率增加超过30次/分钟来测试探针的功能位置。在注入赋形剂（盐水抗坏血酸盐）期间，以0.5、1.2和4Hz的频率进行迷走神经刺激。迷走神经刺激期间的心血管反应进行在线记录。MEAP通过微透析探针直接注入窦房结。在窦房结应用MEAP、二丙诺啡（阿片拮抗剂）以及二丙诺啡与MEAP联合注入期间，重复评估迷走神经介导的心动过缓。通过微透析探针注入窦房结的MEAP使迷走神经介导的心动过缓降低超过一半。用阿片拮抗剂二丙诺啡同时局部阻断这些受体，消除了MEAP的作用，证明了阿片受体的参与。全身注入MEAP导致迷走神经介导的心动过缓降低，与窦房结给药时观察到的情况几乎相同。当用二丙诺啡阻断局部窦房结阿片受体时，MEAP的全身作用被消除。这些数据使我们认为，介导迷走神经介导的心动过缓抑制作用的阿片受体位于窦房结内，极少有（如果有的话）结外或神经节受体参与。
