Differential hemodynamic, metabolic and hormonal effects of morphine and morphine-6-glucuronide.
Differential hemodynamic, metabolic and hormonal effects of morphine and morphine-6-glucuronide.
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吗啡和吗啡-6-葡萄糖醛酸苷对血流动力学、代谢和激素的影响不同。
DOI：
10.1016/0006-8993(94)91962-3
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发表时间：
1994
期刊：
影响因子：
2.9
通讯作者：
Abumrad,NN
中科院分区：
文献类型：
--
作者：
Molina,PE;Hashiguchi,Y;Ajmal,M;Mazza,M;Abumrad,NN
尽管先前已经描述了吗啡的高血糖效应，但尚不清楚这是否是葡萄糖产生增加和/或葡萄糖利用减少的结果，以及这种代谢效应是否随着葡萄糖醛酸化而丧失。本研究评估了吗啡（莫尔）及其代谢产物吗啡6-葡萄糖醛酸苷（莫尔-6 G）对清醒无限制长期插管大鼠的血流动力学（心率、HR和平均动脉压; MABP）、激素和全身葡萄糖代谢的影响。在大鼠中，通过静脉内输注H2O（Con; 5 μl/h）、莫尔（80 μg/h）或莫尔-6 G（1 μg/h）共4 h，对[3- 3 H]葡萄糖进行预充持续静脉输注，评估全身葡萄糖动力学。莫尔给药导致HR显著升高20%，MABP无变化。莫尔-6 G使HR增加14%，MABP无变化。在莫尔给药的60分钟内，还观察到血浆葡萄糖（+23%）、肝葡萄糖产生（Ra; +27-61%）和全身葡萄糖利用（Rd; +31-61%）的显著升高。I. c. v.莫尔-6 G导致H2O输注大鼠的血流动力学、代谢和激素参数。I. c. v.莫尔导致肾上腺素（2倍）、去甲肾上腺素（50%）、皮质酮（97%）显著增加，而血浆胰岛素和胰高血糖素无变化。I. c. v.莫尔-6 G导致去甲肾上腺素（5倍）、肾上腺素（7倍）更显著升高，皮质酮（99%）类似升高，胰高血糖素（40%）适度升高。这些结果表明：（i）MOR诱导的高血糖症是直接中枢（CNS）机制导致肝脏葡萄糖产生增加的结果，（ii）MOR诱导的应激反应在葡萄糖醛酸化的情况下增强至少80倍，（iii）莫尔抑制胰腺葡萄糖刺激的胰岛素释放。
Although the hyperglycemic effect of morphine has been previously described, it is not clear whether this is the result of increased glucose production and/or decreased glucose utilization and if this metabolic effect is lost with glucuronidation. This study assessed the hemodynamic (heart rate; HR and mean arterial blood pressure; MABP), hormonal and whole body glucose metabolic effects of morphine (MOR) and its metabolite morphine 6-glucuronide (MOR-6G) in conscious unrestrained chronically catheterized rats. Whole body glucose kinetics were assessed with a primed constant intravenous infusion of [3-3H]gluccose in rats infused i.c.v. with H2O (Con; 5 μl/h), MOR (80 μg/h) or MOR-6G (1 μg/h) for a total of 4 h. MOR administration resulted in a significant 20% elevation in HR and no change in MABP. MOR-6G produced a 14% increase in HR and no change in MABP. A significant rise in plasma glucose (+23%), hepatic glucose production (Ra; +27–61%) and whole body glucose utilization (Rd; +31–61%) was also observed within 60 min of MOR administration. I.c.v. MOR-6G resulted in hemodynamic, metabolic and hormonal parameters of H2O infused rats. I.c.v. MOR resulted in a significant increases in epinephrine (2-fold), norepinephrine (50%), corticosterone (97%) with no alterations in plasma insulin and glucagon. I.c.v. MOR-6G resulted in more marked elevations in norepinephrine (5-fold), epinephrine (7-fold) and similar elevation in corticosterone (99%) and modest elevation of glucagon (40%). These results indicate that (i) MOR-induced hyperglycemia is the result of direct central (CNS) mechanisms that result in increased hepatic glucose production, (ii) MOR-induced stress response is enhanced at least 80-fold with glucuronidation, and (iii) MOR inhibits the pancreatic glucose-stimulated insulin release.