5-羟色胺对断奶仔鼠应激腹泻的影响

目的探讨断奶仔鼠应激性腹泻发生与5-羟色胺(5-HT)的相关性及断奶仔鼠应激性腹泻的发生机制。方法将72只雄性21 d断奶ICR小鼠随机分为6组,分别为正常对照组、氢溴酸西酞普兰(CH)对照组、对氯苯丙氨酸(PCPA)对照组、应激腹泻组、CH+应激腹泻组及PCPA+应激腹泻组。腹腔注射给药组(CH 10 mg/kg或PCPA 300mg/kg)处理4h后进行应激腹泻处理,即给予番泻叶(0.4 kg/L)按15ml/kg体重灌胃+后肢束缚应激处理(持续4h),其对照组分别给予相同剂量的生理盐水。处理第5天,检测血糖值、小鼠血浆皮质酮(Cort)、5-HT含量和分布的变化。结果与对照组相比,应激腹泻组和CH对照组小鼠血浆和肠道5-HT含量、血糖值和血浆Cort含量升高,腹泻评分增加,但是增重显著减小;CH+应激腹泻组较应激腹泻组相比5-HT含量、血糖值和Cort含量和腹泻评分显著增加,增重显著减小。PCPA对照组5-HT含量显著降低,与正常对照组相比除血浆Cort含量增加以外无显著变化;PCPA+应激腹泻组与应激腹泻小鼠相比肠道5-HT含量显著降低,增重升高,血糖值降低,但未达到正常水平。结论断奶仔鼠应激性腹泻伴随5-HT增加,CH引起的肠道5-HT含量升高直接导致并加重断奶仔鼠应激性腹泻,PCPA诱导的5-HT含量降低可减弱小鼠腹泻程度。     

Effects of bromocriptine on receptor binding of methionine-enkephalin

Bromocriptine inhibited the binding of methionine-enkephalin (ENK) to rat striatal synaptic membranes in a dose-dependent fashion. The bromocriptine IC50 was 16 micrometers. hill coefficients of bromocriptine were 0.7 and 0.3, suggesting that an allosteric effect was involved in bromocriptine inhibition of ENK binding to its receptor. These data suggest that at least a part of the therapeutic antiparkinsonian effect f bromocriptine is its allosteric effects on the ENK receptor, which influences the function of striatal dopamine neurons and/or of striatal cholinergic neurons.     

Influence of acute fluid loading on stress-induced hemoconcentration and cardiovascular reactivity

The goal of this study was to assess the possible attenuating effects of oral fluid loading on hematological and hemodynamic factors during acute psychological stress in two separate experiments: Experiment 1 assessed the effects of hypotonic fluid loading (water) and Experiment 2 assessed the effects of isotonic fluid loading (Gatorade). Twenty-eight participants were recruited for Experiment 1, and 28 participants were recruited for Experiment 2. Participants for each experiment completed two test sessions, once in a hypo-hydrated condition (following 12-h fast) and once in a fluid loaded condition (hypotonic or isotonic fluid). During each session, hematocrit (Hct), hemoglobin (Hgb), calculated plasma volume (CPV), heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), cardiac output (CO), stroke volume (SV), and total peripheral resistance (TPR) were assessed during a 10-min resting baseline period, 6-min mental arithmetic (MA) task, and a 16-min recovery period. Results for Experiment 1 revealed that the fluid load condition Hct, Hgb, and HR levels were significantly lower in comparison to the hypo-hydration condition, and that Hct, Hgb, and CPV reactivity was greater during the fluid load condition. Results for Experiment 2 revealed that Hct, Hgb, and TPR were lower and CPV, SBP, SV, and CO were higher during the fluid load condition compared to the hypo-hydration condition and that HR, CO, and TPR reactivity was greater during the fluid load condition. Finally, analytic comparisons between the two fluid types revealed that SV and CO levels were significantly greater at baseline and during MA when isotonic fluid was ingested compared to hypotonic fluid ingestion.     

Modulatory effects of defense and coping on stress-induced changes in endocrine and immune parameters

We examined whether habitual defense and coping affect the response of hormones (ACTH. cortisol, prolactin. endorphins, and noradrenaline) and immune parameters (numbers of T cells. B cells. natural killer [NK] cells, and proliferative responses to mitogens or antigens) to an acute laboratory stressor (i.e., solving a 3-dimensional puzzle and explaining it to a confederate) in 86 male high school teachers. Defense and coping were assessed by Kragh's tachistoscopic Defense Mechanism Test (a measure of perceptual defense) and by 4 questionnaire-based coping styles assessing instrumental mastery-oriented coping, emotion-focused coping, cognitive defense, and defensive hostility. The laboratory stressor per se caused a relative increase in immunological (in particular NK cells) and endocrine (cortisol, prolactin) parameters. Defense and coping, however, significantly codetermined the response to the stressor. In particular, instrumental mastery-oriented coping and perceptual defense were related to stress-induced changes in numbers of B cells and in the pituitary-adrenal hormones. The results indicate that the impact of a mild psychological stressor on the immune and endocrine system depends to a considerable extent on the specific ways people deal with stressors.     

The effect of surgery on plasma beta-endorphin and methionine-enkephalin

Seven women undergoing abdominal hysterectomy under halothane and nitrous oxide analgesia had plasma samples taken before, during and after surgery for assay of adrenocorticotrophin (ACTH), beta-endorphin, beta-lipotrophin and methionine (Met)-enkephalin immunoreactivity. Plasma ACTH, beta-endorphin and beta-lipotrophin all rose in parallel from the start of surgery and were unaffected by postoperative opiate analgesia. Plasma Met-enkephalin concentrations did not change significantly during the course of the surgery and immediate post-operative period, although the variance of the samples increased at the time of the first skin incision. These data indicate that the stress of surgery and post-operative pain, while producing marked elevations of proopiomelanocortin-derived peptides, are not associated with changes in plasma Met-enkephalin. These data exclude a role for circulating Met-enkephalin in the modulation of surgical pain but do not exclude such a role for beta-endorphin.     

Influence of pacing parameters on pacemaker longevity

 This study retrospectively assessed the parameters that affect pulse generator longevity in 78 patients implanted with dual-chamber pacemakers. Longevity was studied in 52 generators: 14 Cosmos II, 17 Relay, 11 Ellite II, and 10 Thera DR. The lifetimes of Cosmos II and Ellite II were significantly prolonged compared to those of Relay and Thera DR. The comparative study was conducted to evaluate the effect of low-impedance leads (ThinLine I, n = 10) on generator longevity compared with a standard lead (Irox, n = 16). No significant variation in pacing threshold was found between the groups. However, the low-impedance group provided significantly lower cell voltage and higher cell impedance during all follow-up periods compared with the standard lead impedance group. The internal current of the pacemaker with rate response and sophisticated diagnostic memory function (Relay, n = 5, and Marathon DR, n = 5) increased significantly compared with the conventional pacemaker (Cosmos II, n = 5). In conclusion, the selection of unnecessary pacing parameters and the selection of low-impedance leads should be avoided in order to extend generator longevity. Received: November 5, 2001 / Accepted: May 30, 2002 Correspondence to:N. Mizutani     

Effect of histamine infusion on circulating methionine-enkephalin and catecholamine concentrations

In 5 normal adult men, histamine was infused i.v. for 5 min at 20 micrograms/kg/h and at 80 micrograms/kg/h on two occasions one week apart. Diastolic blood pressure fell and heart rate, plasma adrenaline and noradrenaline all rose in a dose-dependent manner, but plasma methionine-enkephalin (Met-Enk) concentrations were unchanged. These results indicate that while Met-Enk may be co-stored with catecholamines (CAs) in the adrenal medulla in at least this paradigm, circulating concentrations of CAs may be altered without similar changes in plasma Met-Enk immunoreactivity.     

Effect of liver and renal dysfunction on circulating methionine-enkephalin immunoreactivity

Plasma methionine-enkephalin (Met-Enk) immunoreactivity has been determined in 24 patients with varying degrees of renal impairment and 14 patients with hepatic failure. Plasma Met-Enk immunoreactivity correlated inversely with creatinine clearance (r = −0.71, P < 0.001) but was not affected by even severe hepatic failure in the absence of renal impairment. In two patients, with renal failure and elevated plasma prolactin, administration of naloxone (16 mg) had no effect on circulating prolactin concentrations. These studies indicate that the kidney has a major role in Met-Enk metabolism while the liver does not, and further suggest that elevated circulating endogenous opiates are not responsible for the increased production of prolactin found in renal failure.     

Distribution of methionine-enkephalin in the minipig brainstem

We have studied the distribution of immunoreactive cell bodies and axons are containing methionine-enkephalin in the minipig brainstem. Immunoreactive axons were widely distributed, whereas the distribution of perikarya was less widespread. A high or moderate density of axons containing methionine-enkephalin were found from rostral to caudal levels in the substantia nigra, nucleus interpeduncularis, nucleus reticularis tegmenti pontis, nucleus dorsalis raphae, nucleus centralis raphae, nuclei dorsalis and ventralis tegmenti of Gudden, locus ceruleus, nucleus sensorius principalis nervi trigemini, nucleus cuneatus externalis, nucleus tractus solitarius, nuclei vestibularis inferior and medialis, nucleus ambiguus, nucleus olivaris inferior and in the nucleus tractus spinalis nervi trigemini. Immunoreactive perikarya were observed in the nuclei centralis and dorsalis raphae, nucleus motorius nervi trigemini, nucleus centralis superior, nucleus nervi facialis, nuclei parabrachialis medialis and lateralis, nucleus ventralis raphae, nucleus reticularis lateralis and in the formatio reticularis. We have also described the presence of perikarya containing methionine-enkephalin in the nuclei nervi abducens, ruber, nervi oculomotorius and nervi trochlearis. These results suggest that in the minipig the pentapeptide may be involved in many physiological functions (for example, proprioceptive and nociceptive information; motor, respiratory and cardiovascular mechanisms).     

Dopamine and methionine-enkephalin in human brain

The contents of dopamine (determined radioenzymatically) and methionine-enkephalin (assayed by a radioimmunoassay) were measured in several areas of the human brain. The peptide was principally localized in dopamine-rich structures. In patients with Parkinson's disease, in contrast to the general dopamine deficiency, the reduction in methionine-enkephalin was restricted to the mesencephalon, putamen and lateral pallidum.     

Influence of stimulus parameters on human postural responses

1. The role of sensory information in shaping muscle activation patterns to postural perturbations in humans was investigated by varying velocity, amplitude, or duration of the perturbing stimulus. Ten normal subjects were exposed to 120 backward translations of the support surface under conditions of varying velocities (10-35 cm/s, constant amplitude), varying amplitudes (1.2-12 cm, constant velocity), or varying durations (40-800 ms). The effects of perturbation parameters on movement kinematics and EMG latencies, patterns, and integrated areas in six trunk and leg muscles were examined. Integrated EMG activity was normalized across subjects and the early (first 75 ms), middle (second 75 ms), and late (last 350 ms) components were analyzed separately. 2. Ankle, knee, and hip angle trajectories and surface reactive forces suggest that a relatively consistent movement strategy was scaled to the perturbation velocities and amplitudes applied. 3. Short-duration perturbations (75 ms) evoked a single burst of muscle activity (75-100 ms duration) in gastrocnemius, hamstrings, paraspinal, and rectus abdominis muscles at latencies too long to be explained by simple stretch reflexes. EMG latencies, patterns, and integrated areas were independent of the velocity and amplitude of the short-duration perturbations, suggesting a minimal time to incorporate peripheral velocity information into the triggered response. 4. For translations lasting longer than 75 ms, the integrated areas of the early agonist EMG bursts were positively correlated with stimulus velocity. The integrated area of later, more tonic EMG components were best correlated with stimulus amplitude. These relationships were found in both distal (stretched) muscles and in proximal muscles. Absolute latencies (94-145 ms), intersegmental latencies (18-29 ms), and burst durations (75-100 ms) were not influenced by the velocity or amplitude of the stimulus. 5. These results suggest that the spatial and temporal organization of automatic postural responses may be organized independently of response intensity. Within a particular spatial-temporal pattern, the amount of muscle activation appears to be adjusted by sensory information, which specifies velocity and amplitude of the perturbation.     

Effects of neurotensin, substance P and methionine-enkephalin on colonic motility

The influence of neurotensin, substance P and methionine-enkephalin (met-enkephaline) on proximal and distal colonic motility was studied in anesthetized cats. When administered i.v, at a dose of 14 pmol x kg-1 x min-1, neurotensin increased basal smooth muscle tone and antiperistaltic activity in the proximal colon. After higher doses of neurotensin the basal muscle tone also increased in the distal colon. Substance P at a dose of 17 pmol x kg-1 x min-1 selectively and powerfully stimulated the distal colon, thus causing a mass contraction pattern with a concomitant decrease in peristaltic amplitude. In the proximal part of the colon 17 pmol x kg -1 x min-1 of substance P exerted an inhibitory action on the peristaltic amplitude in animals with a high level of spontaneous activity. In addition, the basal muscle tone was slightly decreased. In animals with sluggish spontaneous activity, however, no effects were detected in the proximal colon. With increasing doses of substance P forceful contractions of the proximal colon were also registered. Met-enkephalin at a dose of 40 pmol x kg-1 x min-1 increased the smooth muscle basal tone with no effect on the peristaltic activity in the proximal or distal segments. The effect on basal tone was blocked by naloxone. Thus, neurotensin, substance P and met-enkephalin have distinct motor actions on the colon. At low doses neurotensin may stimulate the churning and mixing functions of the proximal colon. Substance P exerts its major effects on the distal part with a mass contraction response and met-enkepahlin increases the basal muscle tone equally in the proximal and distal parts of the colon.     

慢性轻度不可预见性应激对大鼠海马内甘丙肽表达的影响

目的:观察慢性轻度不可预见性应激(chronic unpredictable mild stress,CUMS)对大鼠海马甘丙肽(ga-lanin,Gal)蛋白及mRNA表达的影响,探讨Gal在大鼠实验性抑郁症发病过程中的作用机制。方法:将20只健康雄性SD大鼠,随机分为正常组和模型组,每组10只。孤养结合CUMS 21 d建造抑郁症模型,应用旷场试验和糖水偏好试验检测大鼠行为学变化,使用免疫荧光组织化学方法和逆转录多聚酶链反应(RT-PCR)法测定Gal及Gal mRNA的表达。结果:造模后模型组大鼠运动总路程、中央路程、周边路程及糖水摄入量均较正常组偏低(P<0.05);模型组与正常组相比,海马内Gal及Gal mRNA的表达同样降低(P<0.05)。结论:慢性轻度不可预见性应激可使大鼠海马内Gal及Gal mRNA的表达量下降,推测Gal在抑郁发病过程中可能起到神经保护作用。     

Effect of melatonin and methionine-enkephalin on surfacing responses in goldfish.

Intracranial injection of 5 to 20 μg of methionine-enkephalin (M-ENK) increased surfacing responses in a dose-related manner in goldfish. This behavioral effect of M-ENK was completely inhibited by an injection of 8 μg naloxone, indicating that the surfacing response produced by M-ENK was mediated by naloxone-sensitive opiate receptors. The possibility of melatonin affecting opiate receptors directly, or indirectly through M-ENK was examined. The injection of melatonin caused surfacing responses and this effect was inhibited by naloxone. Although the behavioral effect of M-ENK was reduced by inhibition of melatonin synthesis by scotophobin A, the increased inhibition of melatonin synthesis did not cause increased inhibition of the M-ENK effect. It was also found that M-ENK did not affect the activity of the enzyme (hydroxyindole-O-methyltransferase) in vitro, which is responsible for the conversion of N-acetylserotonin to melatonin. The results from these experiments suggested that melatonin may directly (or indirectly through M-ENK) affect opiate receptors.     

Phencyclidine decreases methionine-enkephalin content in rat striatum

The acute administration of phencyclidine induced a decrease in methionine-enkephalin levels in rat striatum, as measured by specific radioimmunoassay. The maximum decrease (about 40% with respect to controls) was obtained at a dose of 20 mg/kg, 30 min after intraperitoneal injection. These results suggest a possible involvement of enkephalins in the central effects of phencyclidine.     

甲硫-脑啡肽对脾交感神经活动的双向调节作用

目的：观察第三脑室微量注射甲硫－脑啡肽对脾交感神经放电活动的影响。方法：用ｕｒｅｔｈａｎｅ和α－ｃｈｌｏｒａｌｏｓｅ麻醉的雄性Ｓｐａｇｕｅ－Ｄａｗｌｅｙ大鼠，于第三脑室分别微量注射Ｍｅｔ－Ｅｎｋ１μｇ和１００μｇ。结果：脾交感神经放电活动的双向调节作用，即微量注射１μｇＭｅｔ－Ｅｎｋ时脾交感神经冲动数会减少，而注射１００μｇＭｅｔ－Ｅｎｋ时脾交感神经冲动数会增多。事先静脉注射阿片受体阻断剂纳络酮（