Acute Immobilization Stress and Intraventricular Injection of CRF Suppress Naloxone-Induced LH Release in Ovariectomized Estrogen-Primed Rats

The present study was undertaken to evaluate the role and possible interaction of the endogenous opioid peptide (EOP) and corticotropin-releasing factor (CRF) in the acute stress-induced suppression of gonadotropin secretion in ovariectomized estrogen-primed rats. An intravenous (i.v.) injection of naloxone (10 or 20  mg/kg), an EOP antagonist, significantly elevated serum luteinizing hormone (LH) levels within 10  min in non-stressed animals. The naloxone-induced LH release was completely eliminated when tested 30  min after the onset of acute immobilization. In a subsequent study, it was found that suppression of the naloxone-induced LH release occurred as early as 5  min after the stress onset, and was still evident 60  min after the end of a 30-min period of immobilization. The effect of naloxone was restored 3  h after liberation of the animal from the 30-min immobilization. An intraventricular (i.c.v.) injection of CRF (1 or 5  μg) also significantly suppressed, in a dose-related manner, the effect of a subsequent i.v. injection of naloxone. However, an i.c.v. injection of α -helical CRF(9-41) (25 or 50  μg), a CRF antagonist, prior to immobilization, could not interfere with the suppressive effect of stress on naloxone-induced LH release. These results suggest that both acute immobilization stress and CRF can inhibit the LH secretory activity without mediation by EOP neurons. However, the stress-related suppression may involve non-CRF mechanism(s).     

小鼠吗啡依赖纳洛酮催促戒断跳跃反应模型的建立

目的建立稳定的小鼠吗啡依赖纳洛酮催促戒断跳跃反应模型。方法小鼠连续皮下注射吗啡,以纳洛酮催促戒断跳跃反应为指标,调整吗啡给予天数(5,6,7,10d)、吗啡累积剂量(360,560,640,945,1100,1105,1200mg/kg)、每日给予吗啡的频数[一天二次(bid),一天三次(tid)]、纳洛酮催促紧前给予吗啡与否、以及纳洛酮剂量(10,20mg/kg),建立四个造模方案包括八个子方案。结果方案A、B2、C2吗啡组小鼠跳跃反应率未达100%;方案B1、C1、D2、D3、D4吗啡组小鼠跳跃次数变异系数较大。方案D1采用小鼠连续皮下注射倍增剂量的吗啡,tid×6d,每日每次剂量分别为5,10,20,40,80,160mg/kg;第7天皮下注射吗啡160mg/kg,3h后腹腔注射纳洛酮10mg/kg,吗啡组小鼠可产生显著的跳跃反应,与对照组比较差异有显著性(P<0.01),且变异系数小(CV为0.22),该方案吗啡依赖小鼠跳跃反应次数适度,离散度小。结论选用方案D1可建立稳定的小鼠戒断跳跃反应模型。     

Effect of naloxone on detrusor-sphincter dyssynergia in the chronic spinal cat

Naloxone, an opioid peptide antagonist, has been reported to facilitate voiding in neurologic bladder disorders, but its effects on the neural micturition reflex arc are poorly understood. We studied the effect of naloxone in 34 male adult cats, spinalized at C5-C6 level 7 to 119 days previously. Each cat served as its own control. The following tests were performed: Urethral pressure profiles, cystosphincterograms with the urethro-vesical junction opened and closed and mechanograms of the detrusor, and the circular and longitudinal urethral muscles. The study included (1) the effects of anesthesia of the bladder and pelvic nerve, as well as that of the urethral and pudendal nerves; (2) the action of naloxone; and (3) the action of oxymorphone. Our results demonstrated that naloxone (1) increased somatic (osteotendinous and nociceptive) reflexes and aggravated spasticity; (2) increased vegetative micturitional and sexual reflexes, in particular the urethra-urethral contraction reflex, aggravating the spasmodic contractions of the external sphincter; and (3) increased the frequency and intensity of the mass reflex. In consequence, we suggest that naloxone is contraindicated in cases of spinal cord lesions with detrusor-sphincter dyssynergia syndrome.     

亮氨酸脑啡肽对脂多糖促血管平滑肌细胞增殖效应的抑制作用

观察亮氨酸脑啡肽和脂多糖对血平滑肌细胞增殖的影响，并观察两者之间的相互作用及阿片受体阻滞剂纳洛酮的影响，方法：实验以离体培养的ＳＤ大鼠胸主动脉ＶＳＭＣ为模型。     

吗啡抑制大鼠多觉型伤害性感受器持续放电

作利用复合致痛剂引起大鼠尾部皮肤多觉型伤害性感受器（ＰＭＮ）持续性放电模型，经股静脉注入吗啡（４ｍｇ／ｋｇ），显抑制ＰＭＮ持续性放电。吗啡抑制ＰＭＮ放电５０％的潜伏期为１０±４．５ｍｉｎ，抑制时程超过３０ｍｉｎ。纳络酮１ｍｇ／ｍｇ ｉｖ，可翻转吗啡的抑制作用。在慢性吗啡耐受大鼠，吗啡几乎失去其抑制作用。吗啡引起的ＰＭＮ放电数变化不呈一致关系。小剂量吗啡（１ｍｇ／ｋｇ）注入支配感受野皮肢的尾动脉     

纳洛酮与山莨菪碱、躯体刺激对内毒素休克狗血流动力学影响的比较

静脉给予纳洛酮2mg/kg期间可使内毒素休克狗的平均动脉压(MAP)、左心室收缩压(LVSP)及其一阶导数(±dp/dt max)和心力环面积(CFU)增加,但对肾血流量(RBF)、尿量及20h的存活率无明显影响。将本实验结果与山莨菪碱、躯体刺激效应进行比较,表明三者中山莨菪碱对休克动物的循环改善作用最明显。     

Reduced ACTH/cortisol responses to naloxone in men with Parkinson's disease

Summary In order to establish whether the inhibitory control exerted by endogenous opioid peptides on ACTH/cortisol secretion changes in patients affected by Parkinson's disease, ten parkinsonian male subjects and eight age matched normal controls were tested with naloxone (4 mg an i.v. bolus plus 10 mg infused in two hours). In a different occasion all subjects were tested with normal saline. Experiments started at 09.00 h. Plasma ACTH and cortisol concentrations showed a slight physiological decline during saline test in both groups. In the normal controls and in the parkinsonian patients both ACTH and cortisol levels were significantly higher after naloxone administration than during saline test. However, both naloxone induced ACTH and cortisol responses were significantly higher in normal than in parkinsonian subjects. In agreement with the well-known opioid deficiency characterizing the parkinsonian brain, these data show a reduced opioid inhibitory control of ACTH/cortisol secretion in patients with Parkinson's disease.     

The effect of naloxone on the preoperative gastric volume and pH

The effect of 4 mg oral naloxone on preoperative gastric volume and pH of gastric aspirate was studied in a double-blind, randomized study. Twenty patients received 10 ml of naloxone (4 mg) mixed with 10 ml of orange juice, and 20 patients received 10 ml of isotonic saline mixed with 10 ml of orange juice, 2 h before surgery. Gastric content was obtained immediately after intubation of the trachea. No significant difference in gastric volume and pH of gastric aspirate was found between the two groups. It is concluded that naloxone does not affect gastric emptying and gastric acid secretion to a degree great enough to protect against aspiration of gastric contents into the lungs.     

吗啡及纳洛酮对淋巴细胞体外增殖的作用(英文)

目的:研究吗啡对不同淋巴细胞增殖的作用及纳洛酮的影响.方法:观察吗啡对未成熟的、静止的及活化的脾脏淋巴细胞体外增殖影响及纳洛酮的阻断作用.结果:吗啡(1×10~(-10)—1×10~(-6)mol L~(-1))能增加Con A诱导的T-细胞的增殖,1 μmol L~(-1)还能促进LPS诱导的B-细胞的增殖,同时这些增强作用都能被纳洛酮50μmol L~(-1)阻断,纳洛酮单独亦能促进活化T-细胞的增殖.而吗啡1×10~(-10)—1×10~(-5)mol L~(-1)对静止的脾脏淋巴细胞及Con A活化的胸腺淋巴细胞的增殖都无影响.但是吗啡1mmol L~(-1)能广泛抑制静止的、LPS活化的脾脏细胞及Con A活化的胸腺,脾脏淋巴细胞增殖,且都不能被纳洛酮阻断.结论:吗啡对活化T-和B-细胞的促进作用是由细胞表面的阿片受体介导的,此阿片受体随着淋巴细胞的成熟和活化而变化,而吗啡1 mmol L~(-1)对淋巴细胞增殖的抑制作用却不是由经典的阿片受体介导的.     

促甲状腺素释放激素拮抗β－内啡肽对心血管的抑制作用

本研究用兔侧脑室给药观察了促甲状腺素释放激素（ＴＲＨ）对β－内啡肽心血管抑制作用的影响。结果表示，β－内啡肽（１０μｇ，ｉｃｖ）能显著抑制兔心血管功能，表现为血压下降，心机收缩力指标如左室收缩压（ＬＶＳＰ），心室内压最大上升和下降速率（±ｄｐ／ｄｔｍａｘ），心肌纤维收缩速度（Ｖｃｅ４０，Ｖｐｍ）和心肌收缩向量环面积（Ｌｐ）明显降低。β－内啡肽的这一作用可被ＴＲＨ（５０μｇ，ｉｃｖ）取消，阿片受体拮抗剂纳洛酮（ＮＡＬ，５０μｇ，ｉｃｖ）也可拮抗β－内啡肽的心血管抑制作用，表明，ＴＲＨ与内源性阿片肽系统有密切关系，结合以前的实验结果提示ＴＲＨ拮抗β－内啡肽的心血管抑制作用有可能是作用在阿片受体上的。