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71.
Effects of orphanin FQ on endomorphin-1 induced analgesia 总被引:4,自引:0,他引:4
Yan-Qing Wang Chong-Bin Zhu Gen-Cheng Wu Xiao-Ding Cao Yan Wang Da-Fu Cui 《Brain research》1999,835(2):241-246
Orphanin FQ (also known as nociceptin) is a 17-amino-acid peptide which acts as a potent endogenous agonist of the orphan opioid receptor-like (ORL1) receptor. Endomorphin-1, a 4-amino-acid peptide discovered recently, is a potent and selective endogenous agonist for the mu-opiate receptor. In the present study, the effect of OFQ or/and endomorphin-1 on the response to noxious thermal stimuli was observed using the tail-flick test in rats. Intracerebroventricular (i.c.v.) administration of OFQ (1, 5 microg) could shorten tail-flick latency; In contrast, intrathecal (i.t.) administration of OFQ (1, 2 or 10 microg) could increase the latency; i.c.v. (1, 2, 5 microg) or i.t. (0.2, 2, 5 microg) administration of endomorphin-1 dose-dependently increased the latency, indicating an analgesic effect. Furthermore, OFQ (0.1-5 microg) when intraventricularly injected together with endomorphin-1 (5 microg), could dose-dependently reverse the analgesia induced by the latter. On the contrary, OFQ (1 microg) intrathecally injected together with endomorphin-1 (0.2 microg) could further increase the tail-flick latency. The results showed that OFQ at the supraspinal level produces hyperalgesia and is antagonistic to endomorphin-1, while at the spinal level it produces analgesia and is synergic with endomorphin-1. Different interaction mechanism between OFQ and endomorphin-1 in the brain and the spinal cord is thus suggested. 相似文献
72.
73.
High density Nociceptin/Orphanin FQ (N/OFQ) and its receptor (NOPr) have been found in the ventrolateral periaqueductal gray (vlPAG), a main output pathway involved in the descending pain-control system. Our previous study demonstrated that the microinjection of N/OFQ into the vlPAG markedly facilitated nociceptive responses of spinal dorsal horn neurons. The aim of the present work was to further provide evidence for the supraspinal mechanisms of action for N/OFQ-mediated nociceptive facilitation by examining the effect of N/OFQ in the vlPAG on neurotransmitter release in the descending pain-control system, including the nucleus raphe magnus (NRM), nucleus reticularis gigantocellularis (NGC) and dorsal horn of the spinal cord. The results showed that the microinjection of N/OFQ into the vlPAG produced robust decreases in 5-hydroxytryptamine (5-HT, serotonin), norepinephrine (NE), and γ-aminobutyric acid (GABA), and increase in glutamate (Glu) release in the spinal dorsal horn. Spinal application of 5-HT, 2-Me-5-HT (5-HT3 receptor agonist), muscimol (GABAA receptor agonist), and baclofen (GABAB receptor agonist) significantly blocked intra-vlPAG-induced facilitation on nociceptive responses. However, the extracellular concentrations of these neurotransmitters in the NRM and NGC exhibited diversity following intra-vlPAG of N/OFQ. In the NRM, intra-vlPAG injection of N/OFQ significantly decreased 5-HT, NE, and Glu, but increased GABA release. Differently, in the NGC, both NE and GABA releases were attenuated by intra-vlPAG of N/OFQ, whereas the concentration of 5-HT and Glu exhibited a trend to increase. These findings provide direct support for the hypothesis that intra-PAG of N/OFQ-induced facilitation of nociceptive responses is associated with the release of 5-HT, NE, and amino acids. 相似文献
74.
孤啡肽对大鼠体内外结肠动力的影响 总被引:2,自引:0,他引:2
目的:探讨孤啡肽受体在结肠运动中的作用. 方法:采用大鼠离体结肠肌条张力测定法、在体结肠肌电测定、炭末推进试验等研究了孤啡肽受体的内源性配基——孤啡肽对大鼠结肠动力的影响.结果:孤啡肽(1-1000 nmol/L)剂量依赖性地引起离体结肠肌条的强直性收缩;孤啡肽(1 μg/ kg)iv诱导在体近端结肠的相位性收缩和基础张力的增加(t=2.41,P=0.02);孤啡肽(3 nmol/ kg)sc加速活性炭悬液通过结肠的转运(48.0± 1.24 vs 43.5±2.63,t=-4.5,P=0.008).结论:孤啡肽通过一个神经性的非阿片受体介导的机制加速大鼠结肠的收缩和转运,孤啡肽在结肠生理功能中起了一定的作用. 相似文献
75.
急性吗啡耐受大鼠脑内孤啡肽含量和释放量变化的研究 总被引:2,自引:0,他引:2
目的:应用放射免疫分析方法检测急性吗啡耐受过程中大鼠脑室灌流液、中脑导水管周围灰质(PAG)及杏仁核中孤啡肽(OFQ)免疫活性(ir)的动态变化。结果:(1)每2小时皮下注射盐酸吗啡1次(7mg/kg),连续注射8次,造成急性吗啡耐受。此组大鼠脑室灌流液中OFQir较生理盐水对照组升高40%,差异显著(P<0.05)。(2)皮下注射吗啡1、6、8次的大鼠PAG中OFQir含量呈逐渐增长趋势,分别较生理盐水组升高9%(P>0.05)、35%(P<0.05)和60%(P<0.01)。(3)皮下注射1次吗啡的大鼠杏仁核中OFQir与生理盐水组相比,降低11%,但无统计学意义;至第8次吗啡注射后较对照组升高41%(P<0.05)。结论:多次注射吗啡能引起大鼠脑内OFQ含量和释放增多,结合以往关于OFQ在脑内对抗吗啡镇痛的事实表明内源性OFQ可能参与急性吗啡耐受的形成。 相似文献
76.
目的研究内囊出血大鼠血浆及心肌组织中孤啡肽、垂体腺苷酸环化酶激活肽(PACAP)含量变化及其在急性心肌损害中的作用。方法建立大鼠内囊出血模型,用放免法测定血浆及心肌组织中孤啡肽、PACAP含量。结果大鼠内囊出血组血浆及心肌组织中孤啡肽含量明显高于对照组(P<0.01);血浆PACAP含量明显高于对照组(P<0.01),而心肌组织中PACAP含量明显低于对照组(P<0.01)。结论孤啡肽、PACAP含量变化在内囊出血后急性心肌损害过程中起重要作用。 相似文献
77.
发现内阿片肽家族的两个新成员:孤啡肽和内吗啡肽 总被引:2,自引:0,他引:2
韩济生 《中国疼痛医学杂志》1997,3(3):129-134
孤啡肽(Orphanin FQ,OFQ)和内吗啡肽(endomorphin)是1995年和1997年发现的两种内阿片肽,它们在痛觉调制中的作用值得加以探讨。 相似文献
78.
Activation of opioid receptor-like 1 receptor (ORL1) by intrathecal administration of orphanin FQ (OFQ), an endogenous ligand for the ORL1 receptor, has been shown to produce antinociception. In addition, we have recently shown gonadal hormone-dependent, sex-specific modulation of acute spinal nociception such that estrogen attenuated OFQ-induced antinociception in the female whereas testosterone was required for the expression of antinociception in the male. However, sex-related differences in the role of OFQ under hyperalgesic conditions are unknown. Hence, we investigated whether OFQ produces sex-specific modulation of mustard oil-induced secondary thermal hyperalgesia in the rat. Mustard oil application to the hind limb significantly reduced the tail-flick latencies (TFL) in male, and ovariectomized (OVX), estradiol treated ovariectomized (OVX + E), proestrous (ProE) and diestrous (DiE) females. Intrathecal administration of OFQ not only attenuated mustard oil-induced decrease in TFLs, i.e. reversed hyperalgesia, but also led to a significant increase in TFLs above the baseline, i.e. produced antinociception in male, OVX, and diestrous rats. However, OFQ failed to alter TFLs in proestrous or OVX + E females, thus these two groups with elevated estrogen levels remained hyperalgesic following mustard oil treatment. These findings demonstrate that OFQ modulates mustard oil-induced secondary hyperalgesia in an estrogen-dependent, sex-specific manner. 相似文献
79.
目的探讨孤啡肽(OFQ)以及单胺类递质与围绝经期抑郁症的关系。方法采用放射免疫法测定58例围绝经期抑郁症妇女(研究纽)和60名健康同龄妇女(对照组)静脉血中孤啡肽及单胺类递质含量。结果研究组和对照组血雌二醇(E2)、血清卵泡雌激素(FSH)、去甲肾上腺素(NE)、5-羟色胺(5-HT)、孤啡肽(OFQ)含量和HAMD总分、KMI评分比较均有显著性差异。研究组OFQ与E2、5-HT含量呈显著负相关(r分别为-0.601及-0.593,P〈0.05);研究组OFQ与FSH、NE含量呈显著正相关(r分别为0.524及0.658,P〈0.05);研究组OFQ与HAMD总分、KMI评分呈显著正相关(r分别为0.854及0.631,P〈0.01)。研究组5-HT、NE与E2、FSH、HAMD总分、KMI评分的相关性无统计学意义(P〈0.05)。结论血浆OFQ水平的变化可能参与围绝经期抑郁症的发病机制,并可能揭示病情的严重程度。 相似文献
80.
Economidou D Cippitelli A Stopponi S Braconi S Clementi S Ubaldi M Martin-Fardon R Weiss F Massi M Ciccocioppo R 《Alcoholism, clinical and experimental research》2011,35(4):747-755
Background: Alcohol withdrawal refers to a cluster of symptoms that may occur from suddenly ceasing the use of alcohol after chronic or prolonged ingestion. These symptoms make alcohol abstinence difficult and increase the risk of relapse in recovering alcoholics. In previous studies, we demonstrated that treatment with Nociceptin/orphanin FQ (N/OFQ) significantly reduces alcohol consumption and attenuates alcohol‐seeking behavior induced by environmental conditioning factors or by stress in rats. In this study, we evaluated whether activation of brain NOP receptors may also attenuate alcohol withdrawal signs in rats. Methods: For this purpose, animals were subjected to a 6‐day chronic alcohol intoxication (by intragastric administration), and at 8, 10, and 12 hours following cessation of alcohol exposure, they were treated intracerebroventricularly (ICV) with N/OFQ (0.0, 1.0, and 3.0 μg/rat). Somatic withdrawal signs were scored after ICV treatment. In a subsequent experiment, to evaluate N/OFQ effects on alcohol withdrawal‐induced anxiety, another group of rats was subjected to ethanol intoxication and after 1 week was tested for anxiety behavior in the elevated plus maze (EPM). In the last experiment, an additional group of rats was tested for anxiety elicited by acute ethanol intoxication (hangover anxiety). For this purpose, animals received an acute dose (3.0 g/kg) of 20% alcohol and 12 hour later were tested in the EPM following ICV N/OFQ (0.0, 1.0, and 2.0 μg/rat). Results: Results showed that N/OFQ significantly reduced the expression of somatic withdrawal signs and reversed anxiety‐like behaviors associated with both chronic and acute alcohol intoxication. N/OFQ did not affect anxiety scores in nondependent animals. Conclusions: These findings suggest that the N/OFQ‐NOP receptor system may represent a promising target for the development of new treatments to ameliorate alcohol withdrawal symptoms. 相似文献