Endorphins and the hypotensive response to stimulation of alpha-receptors in the brainstem by alpha-methylnoradrenaline

Opioid peptide involvement in the fall in blood pressure resulting from stimulation of alpha-receptors in the brainstem has been investigated in the urethane-anaesthetised rat. Unilateral microinjection of alpha-methylnoradrenaline into the nucleus tractus solitarii (NTS) induced a doserelated fall in blood pressure and heart rate. The depressor response induced by the amine was prevented by pretreatment with naloxone, administered either subcutaneously or directly into the nucleus. Pretreatment with antiserum to beta-endorphin, applied locally, also blocked the depressor response, however a similar dilution of antiserum to met-enkephalin was ineffective in this respect. The local application of phentolamine into the n. tractus solitarii caused an initial fall in both blood pressure and heart rate, and blocked the cardiovascular changes induced by alpha-methylnoradrenaline for at least 90 min. Pretreatment with the alpha-receptor antagonist attenuated the fall in blood pressure produced by microinjection of beta-endorphin. These results suggest that the fall in blood pressure observed after administration of alpha-methylnoradrenaline involves a beta-endorphin-like peptide, a probable site of this interaction being the n. tractus solitarii.     

THE ROLE OF β-ENDORPHIN IN THE MECHANISMS OF ISCHEMIC ARRHYTHMIA IN RATS

ＴＨＥＲＯＬＥＯＦβ－ＥＮＤＯＲＰＨＩＮＩＮＴＨＥＭＥＣＨＡＮＩＳＭＳＯＦＩＳＣＨＥＭＩＣＡＲＲＨＹＴＨＭＩＡＩＮＲＡＴＳＨｅＢｅｎ（何奔）；ＺｈｅｎｇＤａｏｓｈｅｎ（郑道声）；ＺｈａｎｇＳｈｉｈｕａ（张世华）；ＷｕＹｉｘｉａｎ（邬亦贤）（Ｄｅｐａｒ...     

SEPARATION OF OPIOID PEPTIDES UTILIZING HIGH PERFORMANCE LIQUID CHROMATOGRAPHY

Chromatographic procedures have been developed for resolving all of the known enkephalins and endorphins on a single column. The effect of eluant pH on the retention times and separation of the enkephalins and β-endorphin was determined. By combining these separations with a sensitive radioreceptor assay it is possible to assay all of the opioid peptides in the pituitary gland or in various regions of the brain from individual small laboratory animals.     

Investigation of pituitary influences on autoanalgesia.

(1) The effect of manipulations of pituitary hormonal systems on several paradigms of analgesia, as assessed by the tail-flick procedure, were investigated. (2) Systemic injection of ACTH did not elicit analgesia at 15, 30 or 60 min post injection. (3) Hypophysectomy had no effect upon analgesia elicited by acute foot shock. (4) Analgesia, elicited by classically conditioning fear to the tail-flick procedure, was slightly potentiated by hypophysectomy. (5) Hypophysectomy also potentiated morphine-induced analgesia at 2 and 3 hr, but not at 15, 30 or 60 min post injection. (6) These data suggest that neurochemical events in addition to pituitary-adrenal activation are necessary to elicit autoanalgesia (behaviorally-induced antinociception) and that CNS changes in opioid peptide activity which accompany autoanalgesia are independent of pituitary endorphins.     

Up-regulation of opiate receptors by opiate antagonists in neuroblastoma-glioma cell culture: The possibility of interaction with guanosine triphosphate-binding proteins

Neuroblastoma-glioma NG108-15 cells that were cultured for 48 h with the opiate antagonist, naloxone, respond to the guanosine 5′-triphosphate (GTP) analogue guanosine 5′-[β,γ-imido]-triphosphate (GMP-PNP) in the binding assay as the control, non-treated, cells. This was observed when the guanyl nucleotide was tested in the presence or absence of sodium chloride and also after subcellular fractionation of the membranes on a sucrose gradient which separated between two receptor-containing fractions. The findings suggest that the increase in δ type enkephalin receptors in naloxone-treated NG108-15 cells does not reflect an alteration in the interaction between the receptor and the adenylate cyclase-GTP-binding protein system.     

钩藤碱对苯丙胺诱导的大鼠条件性位置偏爱的影响及机制探讨

目的 观察钩藤碱对苯丙胺诱导的大鼠条件性位置偏爱的影响,并探讨其机制。方法 将40只雄性SPF级SD大鼠分为空白对照组（A组）、苯丙胺组（B组）、氯胺酮＋苯丙胺组（C组）、钩藤碱＋苯丙胺组（D组）和钩藤碱＋生理盐水组（E组）,每组各8只。分别给予相应药物。第4天将各组大鼠置于条件性位置偏爱箱中并记录其在白箱中的停留时间,同时用脑电超慢涨落分析仪绘制全脑分维参数地形图并检测大鼠脑中内啡肽的水平。结果 氯胺酮和钩藤碱均能消除苯丙胺诱导的大鼠位置偏爱;钩藤碱本身不能引起位置偏爱。A组大鼠的全脑分维参数地形图呈现“脑功能平衡图”,苯丙胺使其完全偏离平衡状态,经氯胺酮或钩藤碱治疗后可恢复。B组大鼠脑内的内啡肽水平明显下降。C、D、E组与A组大鼠脑内内啡肽水平差异无统计学意义。结论 钩藤碱可能通过提高脑中内啡肽含量治疗苯丙胺诱导的条件性位置偏爱;且钩藤碱本身无精神依赖性。     

阻塞性睡眠呼吸暂停低通气综合征患者血浆VIP和β-EP水平的变化及意义

目的：通过检测血管活性肠肽（VIP）和β-内啡肽（β-EP）在阻塞性睡眠呼吸暂停低通气综合征（OSAHS）患者血浆中的含量,探讨二者在OSAHS发病过程中的病理生理意义,进而探讨二者可能的相互作用的机制.为OSAHS的病因诊断和治疗提供新的理论依据.方法：实验对象为45例经过多导睡眠监潮（礤G）筛选的OSAHS患者,以呼吸暂停低通气指数（Am）为标准进行分度,其中轻中度组29例,重度组16例.对照组为经PSG监测排除OSAHS诊断的健康成人志愿者15例.采用酶联免疫吸附法（EUSA）分别检测OSAHS组和正常对照组的血浆中VIP和β-EP的浓度.对VIP与β-EP的表达结果及二者的相关性进行统计学分析.结果：OSAHS患者血浆中V艘为高表达,表达差异具有显著性（P＜0.01）.OSAHS轻中度组的ⅥP浓度显著高于对照组（P＜0.01）;重度OSAHS组的VIP浓度明显高于轻中度OSAHS组（P＜0.01）.OSAHS患者血浆中β-腰为高表达,表达差异具有显著性（P＜0.01）.OSAHS轻中度组的β-EP浓度显著高于对照组（P＜0.01）;重度OSAHS组的β-EP浓度明显高于轻中度OSAHS组（P＜0.01）.在OSAHS重度组Ⅷ与β-EP的表达呈正相关,且差异有统计学意义（P＜0.01）.结论：VIP和β-EP在OSAHS患者血浆中均存在高表达,且重度组明显高于轻中度组,说明二者在OSAHS的疾病发生发展的过程中发挥了重要作用.VIP作为具有舒张血管作用的神经肽类物质,可以改善组织缺氧,但其过度表达可导致血管通透性增加,局部组织水肿,加重OSAHS的病情.β-EP的高表达,可构成缺氧、β-EP升高、呼吸抑制、缺氧这一恶性循环,导致OSAHS的病情的复杂化.VIP和β-EP两种神经肽在参与OSAHS疾病发生发展过程中呈现显著的正相关性.     

Differential regulation of prohormone convertase 1/3, prohormone convertase 2 and phosphorylated cyclic-AMP-response element binding protein by short-term and long-term morphine treatment: implications for understanding the "switch" to opiate addiction

Drug addiction is a state of altered brain reward and self-regulation mediated by both neurotransmitter and hormonal systems. Although an organism's internal system attempts to maintain homeostasis when challenged by exogenous opiates and other drugs of abuse, it eventually fails, resulting in the transition from drug use to drug abuse. We propose that the attempted maintenance of hormonal homeostasis is achieved, in part, through alterations in levels of processing enzymes that control the ratio of active hormone to pro-hormone. Two pro-hormone convertases, PC1/3 and PC2 are believed to be responsible for the activation of many neurohormones and expression of these enzymes is dependent on the presence of a cyclic-AMP response element (CRE) in their promoters. Therefore, we studied the effects of short-term (24-h) and long-term (7-day) morphine treatment on the expression of hypothalamic PC1/3 and PC2 and levels of phosphorylated cyclic-AMP-response element binding protein (P-CREB). While short-term morphine exposure down-regulated, long-term morphine exposure up-regulated P-CREB, PC1/3 and PC2 protein levels in the rat hypothalamus as determined by Western blot analysis. Quantitative immunofluorescence studies confirmed these regulatory actions of morphine in the paraventricular and dorsomedial nucleus of the hypothalamus. Specific radioimmunoassays demonstrated that the increase in PC1/3 and PC2 levels following long-term morphine led to increased TRH biosynthesis as evidence by increased TRH/5.4 kDa C-terminal proTRH-derived peptide ratios in the median eminence. Promoter activity experiments in rat somatomammotrope GH3 cells containing the mu-opioid receptor demonstrated that the CRE(s) in the promoter of PC1/3 and PC2 is required for morphine-induced regulation of PC1/3 and PC2. Our data suggest that the regulation of the prohormone processing system by morphine may lead to alterations in the levels of multiple bioactive hormones and may be a compensatory mechanism whereby the organism tries to restore its homeostatic hormonal milieu. The down-regulation of PC1/3, PC2 and P-CREB by short-term morphine and up-regulation by long-term morphine treatment may be a signal mediating the switch from drug use to drug abuse.     

Cyclo(Gly-Gln) inhibits the cardiorespiratory depression produced by β-endorphin and morphine

Glycyl-

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-glutamine (Gly-Gln; β-endorphin_30–31) is an endogenous dipeptide that is synthesized through the post-translational processing of β-endorphin. Previously, we showed that Gly-Gln inhibits the hypotension and respiratory depression produced by central β-endorphin administration. In this study, we tested whether cyclo(Gly-Gln), a non-polar, cyclic Gly-Gln derivative, was similarly effective following intracerebro-ventricular (i.c.v.) or intra-arterial (i.a.) administration to pentobarbital-anesthetized rats pretreated with β-endorphin (0.5 nmol i.c.v.). Intracerebroventricular cyclo(Gly-Gln) (0.3, 0.6 or 1.0 nmol) injection produced a dose-dependent inhibition of β-endorphin-induced hypotension, but not bradycardia, with a potency similar to that of Gly-Gln. Cyclo(Gly-Gln) (5 mg/kg) was also effective following i.a. injection and significantly attenuated the fall in arterial pressure elicited by i.c.v. β-endorphin, consistent with evidence that cyclic dipeptides permeate the blood–brain barrier; i.a. Gly-Gln was ineffective. Intra-arterial cyclo(Gly-Gln) (5 mg/kg) and i.c.v. Gly-Gln (10 nmol) also attenuated the hypotension and respiratory depression induced by morphine (50 or 100 nmol i.c.v.). Cyclo(Gly-Gln) (0.5, 5.0 or 50.0 mg/kg i.a.) had no effect on arterial pressure or heart rate when given alone. These findings indicate that cyclo(Gly-Gln) is a biologically active peptide capable of reversing the cardiorespiratory depression produced by β-endorphin or morphine.     

社会主义核心价值观大众化的社会心理路径探析

目的 探究氢化可的松(HYD)对新生期结直肠扩张所致的慢性功能性内脏痛大鼠的痛敏反应的影响及其可能的作用途径.方法 SD大鼠出生后第8～14天行结直肠扩张,8周龄后采用腹壁撤退反射评分(AWR)和痛阈测定筛选出具有慢性内脏痛的肠易激综合征(IBS)大鼠,并随机分为4组:生理盐水组、低剂量、中剂量和高剂量HYD组;未经结直肠扩张处理的大鼠为对照组.通过AWR和痛阈测定尾静脉注射HYD前后大鼠痛敏反应程度变化;采用酶联免疫吸附法测定大鼠血清中皮质醇的含量及脊髓胸腰段和腰骶段内啡肽、脑啡肽的含量;行旷场实验测定大鼠心理焦虑程度.结果(1)IBS组大鼠血清中皮质醇的含量显著低于对照组大鼠(P<0.05);(2)IBS组大鼠注射中剂量和低剂量HYD后痛阈均值比注射前显著升高(P<0.05);(3)与生理盐水组比较,低剂量HYD组大鼠脊髓胸腰段内啡肽、脑啡肽含量显著升高(P<0.05);(4)旷场实验显示,IBS组大鼠注射低剂量HYD后大鼠运动总路程增加,平均速度加快(P<0.05).结论 一定剂量的HYD能减轻大鼠的痛敏反应和焦虑抑郁行为,其机制可能与脊髓胸腰段内啡肽、脑啡肽含量变化有关.