Pfeiffer A, Feuerstein G, Kopin I J, Faden A I
J Pharmacol Exp Ther. 1983 Jun;225(3):735-41.
Relatively selective mu-, delta- and kappa-opiate agonists were microinjected into anterior hypothalamic and septal brain regions of the unanesthetized rat in order to investigate the potential role of specific opiate receptors in central cardiovascular regulation. Low doses (0.2-3 nmol) of both [D-Ala2,MePhe4,Gly-(ol)5] enkephalin (DAGO, mu-agonist) and [D-Ala2,D-Leu5]enkephalin (DADL, delta-agonist) caused dose-dependent increases in blood pressure and heart rate which were naloxone reversible. Higher doses (7.5-30 nmol) of DAGO and DADL produced pressor responses but had little effect on heart rate. The kappa-agonist MR 2034 had no effect on cardiovascular parameters at these doses. DAGO but not MR 2034 also depressed respiration at the higher doses resulting in hypoxia, hypercapnia and acidosis while DADL only slightly depressed respiration. DAGO was approximately 10-fold more potent than DADL in eliciting cardiovascular and respiratory responses. These findings implicate mu-receptors in mediating the cardiovascular and respiratory effects of opiates at anterior hypothalamic sites.
为了研究特定阿片受体在中枢心血管调节中的潜在作用,将相对选择性的μ、δ和κ阿片激动剂微量注射到未麻醉大鼠的下丘脑前部和脑隔区。低剂量(0.2 - 3纳摩尔)的[D - Ala2,MePhe4,Gly - (ol)5]脑啡肽(DAGO,μ激动剂)和[D - Ala2,D - Leu5]脑啡肽(DADL,δ激动剂)引起血压和心率呈剂量依赖性增加,且可被纳洛酮逆转。较高剂量(7.5 - 30纳摩尔)的DAGO和DADL产生升压反应,但对心率影响很小。在这些剂量下,κ激动剂MR 2034对心血管参数无影响。较高剂量时,DAGO而非MR 2034还会抑制呼吸,导致缺氧、高碳酸血症和酸中毒,而DADL仅轻微抑制呼吸。在引发心血管和呼吸反应方面,DAGO的效力约是DADL的10倍。这些发现表明μ受体在前下丘脑部位介导阿片类药物的心血管和呼吸作用。