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抗脑啡肽酶D-苯丙氨酸对应激诱导镇痛的拮抗作用。

Antagonism of stress-induced analgesia by D-phenylalanine, an anti-enkephalinase.

作者信息

Bodnar R J, Lattner M, Wallace M M

出版信息

Pharmacol Biochem Behav. 1980 Dec;13(6):829-33. doi: 10.1016/0091-3057(80)90215-4.

DOI:10.1016/0091-3057(80)90215-4
PMID:7208549
Abstract

Methionine- and leucine-enkephalin produce mild and transient analgesic effects, presumably because of enzymatic degradation. Administration of high (250 mg/kg) doses of D-phenylalanine retards the degradation process and elicits analgesia which is reversed by naloxone and which summates with electroacupuncture analgesia. The present study evaluated D-phenylalanine's dose-dependent effects upon a non-opioid analgesic treatment, cold-water swims (CWS), and compared this with morphine. following determination of flinch-jump baselines, three groups of rats received respectively either 25, 50 or 100 mg/kg of D-phenylalanine intraperitoneally in three conditions: alone, with CWS (2 degrees C for 3.5 min), and with morphine (5 mg/kg, SC). Parallel controls with saline were also tested. Simultaneous exposure with each minimally analgesic dose of D-phenylalanine reduced significantly the analgesic, but not hypothermic effects of CWS. By contrast, morphine analgesia was unaffected by D-phenylalanine. These data provide further support that different pain-inhibitory systems mediate CWS and morphine analgesia and suggest that activation of one system is capable of exerting collateral inhibition upon the other.

摘要

甲硫氨酸脑啡肽和亮氨酸脑啡肽产生轻微且短暂的镇痛作用,推测是由于酶促降解。给予高剂量(250毫克/千克)的D-苯丙氨酸会延缓降解过程并引发镇痛作用,这种镇痛作用可被纳洛酮逆转,并且与电针镇痛作用相加。本研究评估了D-苯丙氨酸对一种非阿片类镇痛治疗——冷水游泳(CWS)的剂量依赖性作用,并将其与吗啡进行比较。在确定退缩-跳跃基线后,三组大鼠在三种情况下分别腹腔注射25、50或100毫克/千克的D-苯丙氨酸:单独注射、与CWS(2摄氏度,持续3.5分钟)同时进行、与吗啡(5毫克/千克,皮下注射)同时进行。还测试了用生理盐水作为平行对照。与每个最低镇痛剂量的D-苯丙氨酸同时接触可显著降低CWS的镇痛作用,但不影响其降温作用。相比之下,吗啡镇痛作用不受D-苯丙氨酸影响。这些数据进一步支持了不同的疼痛抑制系统介导CWS和吗啡镇痛作用,并表明一个系统的激活能够对另一个系统产生旁侧抑制作用。

相似文献

1
Antagonism of stress-induced analgesia by D-phenylalanine, an anti-enkephalinase.抗脑啡肽酶D-苯丙氨酸对应激诱导镇痛的拮抗作用。
Pharmacol Biochem Behav. 1980 Dec;13(6):829-33. doi: 10.1016/0091-3057(80)90215-4.
2
Naloxazone and pain-inhibitory systems: evidence for a collateral inhibition model.
Pharmacol Biochem Behav. 1982 Dec;17(6):1175-9. doi: 10.1016/0091-3057(82)90116-2.
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Analgesic responses elicited by endogenous enkephalins (protected by mixed peptidase inhibitors) in a variety of morphine-sensitive noxious tests.内源性脑啡肽(受混合肽酶抑制剂保护)在多种对吗啡敏感的伤害性试验中引发的镇痛反应。
Eur J Pharmacol. 1991 Jan 10;192(2):253-62. doi: 10.1016/0014-2999(91)90050-z.
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[The enkephalinase mechanisms of the resistance and tolerance to the analgesic effect of morphine in rats. Differences in the effects of the action of D-phenylalanine in morphine-sensitive, morphine-tolerant and morphine-resistant rats].[大鼠对吗啡镇痛作用的抗性和耐受性的脑啡肽酶机制。D-苯丙氨酸对吗啡敏感、吗啡耐受和吗啡抗性大鼠作用效果的差异]
Biull Eksp Biol Med. 1993 Jul;116(7):54-6.
5
The effects of D-phenylalanine and its derivatives on enkephalin degradation in vitro: relation to analgesia and attenuation of the morphine withdrawal syndrome.D-苯丙氨酸及其衍生物对脑啡肽体外降解的影响:与镇痛及吗啡戒断综合征减轻的关系。
Pol J Pharmacol Pharm. 1986 Jan-Feb;38(1):41-9.
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Opiate and peptide interaction: effect of enkephalins on morphine analgesia.阿片类药物与肽的相互作用:脑啡肽对吗啡镇痛的影响。
Eur J Pharmacol. 1980 Nov 21;68(2):181-5. doi: 10.1016/0014-2999(80)90319-2.
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Differential effects of leucine and methionine enkephalin on morphine-induced analgesia, acute tolerance and dependence.亮氨酸脑啡肽和蛋氨酸脑啡肽对吗啡诱导的镇痛、急性耐受及依赖性的不同作用。
J Pharmacol Exp Ther. 1979 Jan;208(1):86-90.
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Mu and delta receptors: their role in analgesia in the differential effects of opioid peptides on analgesia.μ受体和δ受体:它们在阿片肽镇痛差异效应中的镇痛作用。
Life Sci. 1982 Apr 26;30(17):1443-55. doi: 10.1016/0024-3205(82)90558-6.
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In vivo antagonism by naloxone of morphine, beta-endorphin and a synthetic enkephalin analog.纳洛酮对吗啡、β-内啡肽及一种合成脑啡肽类似物的体内拮抗作用
J Pharmacol Exp Ther. 1978 Dec;207(3):878-83.
10
Epileptic properties of leucine- and methionine-enkephalin: comparison with morphine and reversibility by naloxone.亮氨酸脑啡肽和甲硫氨酸脑啡肽的癫痫特性:与吗啡的比较及纳洛酮的可逆性作用
Brain Res. 1978 May 26;147(2):327-37. doi: 10.1016/0006-8993(78)90843-0.

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