Bach F W, Yaksh T L
Anesthesiology Research Laboratory, University of California San Diego, La Jolla 92093-0818, USA.
Brain Res. 1995 Sep 4;690(2):167-76. doi: 10.1016/0006-8993(95)00600-u.
To examine the resting and evoked release of the endogenous opioid peptides beta-endorphin and Met-enkephalin from brain, we examined the levels of the respective immunoreactivities in the lateral ventricle-cisterna magna perfusate of the halothane-anesthetized rat. Ten Hz but not 100 Hz stimulation in the arcuate nucleus (ARC) of the hypothalamus released beta-endorphin immunoreactivity (beta-EPir) to the perfusate, whereas 100 Hz but not 10 Hz stimulation in the periaqueductal gray (PAG) of the mid brain released Met-enkephalin immunoreactivity (MEir). MEir was not released by stimulation in ARC and beta-EPir was not released by stimulation in PAG. Characterization of the released beta-EPir and MEir by high performance liquid chromatography showed that authentic beta-endorphin and Met-enkephalin were the major constituents of beta-EPir and MEir, respectively. Systemic administration of the dopaminergic antagonist haloperidol increased plasma, but not perfusate levels of beta-EPir. Both the opioid antagonist naloxone and the NMDA antagonist MK-801 failed to affect beta-EPir or MEir release. ARC and PAG stimulated inhibited a nociceptive reflex (tail-dip in 52.5 degrees C water), and naloxone did not reliably reverse this inhibition. These data support the previously suggested possibility of opioid mediation of stimulation induced analgesia, although we were unable to confirm the theory by naloxone reversibility in this study. Furthermore, the data support the assumption that measurement of opioid peptides in cerebrospinal fluid is a relevant approach in research aimed at elucidating the physiological and pathophysiological roles of endogenous opioid peptides.
为了研究内源性阿片肽β-内啡肽和甲硫氨酸脑啡肽在静息状态及诱发状态下从脑内的释放情况，我们检测了氟烷麻醉大鼠侧脑室-大脑大池灌流液中各自的免疫反应水平。下丘脑弓状核（ARC）以10Hz而非100Hz刺激时，灌流液中β-内啡肽免疫反应性（β-EPir）释放增加；而中脑导水管周围灰质（PAG）以100Hz而非10Hz刺激时，甲硫氨酸脑啡肽免疫反应性（MEir）释放增加。ARC刺激不释放MEir，PAG刺激不释放β-EPir。通过高效液相色谱对释放的β-EPir和MEir进行表征，结果显示，真正的β-内啡肽和甲硫氨酸脑啡肽分别是β-EPir和MEir的主要成分。多巴胺能拮抗剂氟哌啶醇全身给药可增加血浆中β-EPir水平，但不增加灌流液中β-EPir水平。阿片拮抗剂纳洛酮和NMDA拮抗剂MK-801均未能影响β-EPir或MEir的释放。刺激ARC和PAG可抑制伤害性反射（52.5℃水中甩尾），且纳洛酮不能可靠地逆转这种抑制作用。这些数据支持了先前提出的阿片类物质介导刺激诱导镇痛作用的可能性，尽管在本研究中我们未能通过纳洛酮可逆性来证实该理论。此外，这些数据支持这样一种假设，即脑脊液中阿片肽的测量是旨在阐明内源性阿片肽生理和病理生理作用的研究中的一种相关方法。
