Szeto H H, Cheng P Y, Soong Y, Wu D L
Department of Pharmacology, Cornell University Medical College, New York, New York 10021, USA.
Am J Physiol. 1995 Sep;269(3 Pt 2):R702-7. doi: 10.1152/ajpregu.1995.269.3.R702.
The mechanisms by which opioids increase or decrease fetal breathing remain unclear. Fetal plasma glucose is known to modulate breathing activity, and opioids have been reported to alter glucose regulation in the adult. In this study, we investigated whether alterations in fetal breathing by opioids may be explained by changes in plasma glucose levels. We compared the effects of morphine (nonselective), [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin (DAMGO, mu-selective), and [D-Pen2,D-Pen5]enkephalin (DPDPE, delta-selective) on fetal breathing and plasma glucose in unanesthetized fetal sheep. Whereas morphine at 1.2 and 5.0 mg/h iv resulted in an increase in breath number (P < 0.01), plasma glucose was decreased after 1.2 mg/h (P = 0.006) but increased after 5.0 mg/h (P = 0.008). DAMGO (100 micrograms/h icv) increased plasma glucose (P = 0.001) but reduced fetal breathing (P < 0.001). In contrast, DPDPE (30 micrograms/h icv) increased fetal breathing (P = 0.026) but had no effect on plasma glucose concentration. These data demonstrate that the actions of opioids on fetal glucose regulation and breathing are dependent on dose and receptor selectivity. However, there is no relationship between the effects of opioids on fetal breathing and plasma glucose concentration.
阿片类药物增加或减少胎儿呼吸的机制尚不清楚。已知胎儿血浆葡萄糖可调节呼吸活动，且有报道称阿片类药物会改变成人的葡萄糖调节。在本研究中，我们调查了阿片类药物引起的胎儿呼吸改变是否可以用血浆葡萄糖水平的变化来解释。我们比较了吗啡（非选择性）、[D - 丙氨酸2，N - 甲基苯丙氨酸4，甘氨酸5 - 醇]脑啡肽（DAMGO，μ - 选择性）和[D - 青霉胺2，D - 青霉胺5]脑啡肽（DPDPE，δ - 选择性）对未麻醉的胎羊胎儿呼吸和血浆葡萄糖的影响。静脉注射1.2和5.0mg/h的吗啡会导致呼吸次数增加（P < 0.01），1.2mg/h后血浆葡萄糖降低（P = 0.006），但5.0mg/h后升高（P = 0.008）。脑室内注射100μg/h的DAMGO会使血浆葡萄糖升高（P = 0.001），但会减少胎儿呼吸（P < 0.001）。相比之下，脑室内注射30μg/h的DPDPE会增加胎儿呼吸（P = 0.026），但对血浆葡萄糖浓度没有影响。这些数据表明，阿片类药物对胎儿葡萄糖调节和呼吸的作用取决于剂量和受体选择性。然而，阿片类药物对胎儿呼吸和血浆葡萄糖浓度的影响之间没有关系。
