Cheng P Y, Wu D, Soong Y, McCabe S, Decena J A, Szeto H H
Department of Pharmacology, Cornell University Medical College, New York, New York 10021.
Am J Physiol. 1993 Aug;265(2 Pt 2):R433-8. doi: 10.1152/ajpregu.1993.265.2.R433.
Recent evidence suggests that administration of low doses of morphine causes respiratory stimulation, along with a more active electroencephalogram (EEG) in the fetal lamb. The present study used selective opioid agonists and antagonists to determine the role mu 1- and delta-opioid receptor subtypes play in the response as well as determine if endogenous opioid peptides exert a tonic influence at the mu 1- and delta-opioid receptors to maintain normal EEG and respiratory activity under control, physiological conditions. Both morphine (2.5 mg/h iv) and [D-Pen2,D-Pen5]enkephalin (DPDPE) (46 nmol/h icv) resulted in a significant activation of fetal EEG, which was blocked by naloxonazine (NALZ, mu 1-opioid antagonist) and naltrindole (NTI, delta-opioid antagonist), respectively. Administration of NALZ alone, but not NTI, resulted in a slowing of the EEG. Morphine and [D-Ala2]deltorphin I (0.36 nmol/h icv) significantly increased breath number and were blocked by NALZ and NTI respectively. Both NALZ and NTI alone resulted in a reduction in breath number. These results suggest that the activation of the delta- or mu 1-opioid receptors will stimulate fetal respiratory and EEG activity. Furthermore, the endogenous opioids play a tonic role at both the delta- and mu 1-opioid receptors in the regulation of respiratory timing and EEG activity.
最近的证据表明，低剂量吗啡给药会引起呼吸刺激，同时胎羊脑电图（EEG）更为活跃。本研究使用选择性阿片类激动剂和拮抗剂来确定μ1和δ阿片受体亚型在该反应中的作用，并确定内源性阿片肽在μ1和δ阿片受体上是否发挥紧张性影响，以在对照生理条件下维持正常的脑电图和呼吸活动。吗啡（2.5毫克/小时静脉注射）和[D-青霉胺2，D-青霉胺5]脑啡肽（DPDPE）（46纳摩尔/小时脑室内注射）均导致胎儿脑电图显著激活，分别被纳洛嗪（NALZ，μ1阿片拮抗剂）和纳曲吲哚（NTI，δ阿片拮抗剂）阻断。单独给予NALZ而非NTI会导致脑电图减慢。吗啡和[D-丙氨酸2]强啡肽I（0.36纳摩尔/小时脑室内注射）显著增加呼吸次数，分别被NALZ和NTI阻断。单独给予NALZ和NTI均导致呼吸次数减少。这些结果表明，δ或μ1阿片受体的激活将刺激胎儿呼吸和脑电图活动。此外，内源性阿片类物质在调节呼吸节律和脑电图活动方面，在δ和μ1阿片受体上均发挥紧张性作用。
