Owen M D, Unal C B, Callahan M F, Trivedi K, York C, Millington W R
Department of Anesthesiology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
Am J Physiol Regul Integr Comp Physiol. 2000 Nov;279(5):R1944-8. doi: 10.1152/ajpregu.2000.279.5.R1944.
Glycyl-glutamine (Gly-Gln; beta-endorphin(30-31)) is an endogenous dipeptide that is synthesized through the posttranslational processing of beta-endorphin in brain stem regions that control respiration and autonomic function. This study tested the hypothesis that Gly-Gln administration to conscious rats will prevent the respiratory depression caused by morphine without affecting morphine antinociception. Rats were administered Gly-Gln (1-100 nmol) or saline (10 microl) intracerebroventricularly followed, 5 min later, by morphine (40 nmol icv). Arterial blood gases and pH were measured immediately before Gly-Gln and 30 min after morphine injection. Gly-Gln pretreatment inhibited morphine-induced hypercapnia, hypoxia, and acidosis significantly. The response was dose dependent and significant at Gly-Gln doses as low as 1 nmol. In contrast, Gly-Gln (1-300 nmol) had no effect on morphine-evoked antinociception in the paw withdrawal test. When given alone to otherwise untreated animals, Gly-Gln did not affect nociceptive latencies or blood gas values. These data indicate that Gly-Gln inhibits morphine-induced respiratory depression without compromising morphine antinociception.
甘氨酰谷氨酰胺（Gly-Gln；β-内啡肽(30 - 31)）是一种内源性二肽，它通过在控制呼吸和自主功能的脑干区域对β-内啡肽进行翻译后加工而合成。本研究检验了如下假设：向清醒大鼠给予甘氨酰谷氨酰胺可预防吗啡引起的呼吸抑制，而不影响吗啡的镇痛作用。给大鼠脑室内注射甘氨酰谷氨酰胺（1 - 100纳摩尔）或生理盐水（10微升），5分钟后，再脑室内注射吗啡（40纳摩尔）。在注射甘氨酰谷氨酰胺之前以及注射吗啡后30分钟立即测量动脉血气和pH值。甘氨酰谷氨酰胺预处理可显著抑制吗啡诱导的高碳酸血症、低氧血症和酸中毒。该反应呈剂量依赖性，在低至1纳摩尔的甘氨酰谷氨酰胺剂量下即有显著效果。相比之下，在爪部撤离试验中，甘氨酰谷氨酰胺（1 - 300纳摩尔）对吗啡诱发的镇痛作用没有影响。当单独给予未经其他处理的动物时，甘氨酰谷氨酰胺不影响痛觉潜伏期或血气值。这些数据表明，甘氨酰谷氨酰胺可抑制吗啡诱导的呼吸抑制，而不损害吗啡的镇痛作用。
