Diurnal beta-endorphin changes in human cerebrospinal fluid

Plasma and cerebrospinal fluid (CSF) beta-endorphin levels were determined by a RIA method in seven hydrocephalic male patients. The samples were simultaneously collected every two hours from 8 AM to 12 midnight and every hour from 1 AM to 7 AM. In both plasma and CSF beta-endorphin levels showed significant time-related variations during the 24 hour period. These results suggest the existence of diurnal CSF beta-endorphin variations analogous to those observed in plasma.     

Possible involvement of endogenous beta-endorphin in the pathophysiological mechanisms of Pichinde virus-infected guinea pigs.

Previously, we demonstrated that naloxone, an opiate antagonist, prolonged survival of strain 13 guinea pigs infected with Pichinde virus. Thus, endogenous opiates may be involved in the pathogenesis of this viral disease. To determine whether endogenous opiate levels were affected by Pichinde viral infection, beta-endorphin concentrations in plasma and cerebrospinal fluid (CSF) of normal and infected strain 13 guinea pigs were measured by radioimmunoassay. Cerebrospinal fluid beta-endorphin concentrations were 78.0 +/- 13.2 pg/ml on postinoculation day (PID) 7, 59.0 +/- 5.6 pg/ml on PID 12, and 58.8 +/- 5.4 pg/ml on PID 14. These values were significantly higher than baseline levels of CSF beta-endorphin: 30.8 +/- 1.9 pg/ml. Plasma beta-endorphin concentrations of infected animals increased significantly to 202.1 +/- 17.9 pg/ml on PID 7 and to 154.2 +/- 21.4 pg/ml on PID 12 from a mean baseline value of 84.2 +/- 13.1 pg/ml. After a primer intravenous injection of beta-endorphin (10, 15, or 30 micrograms/kg), followed by constant infusion of beta-endorphin (15, 45, or 90 micrograms/kg.hr) to control noninfected guinea pigs, heart rate (except with the lowest dose) and mean blood pressure decreased markedly. Under these experimental conditions, concentrations of plasma and CSF beta-endorphin increased simultaneously with different magnitude. Because both Pichinde viral infection and beta-endorphin administration produced a similar trend of cardiovascular disturbances, leading to hypotension and bradycardia, increased concentrations of plasma and CSF beta-endorphin may play a partial role in the pathophysiological mechanisms of Pichinde virus infection.     

ACTH, corticosterone and beta-endorphin in the blood plasma of rats under prolonged immobilization stress

Radioimmunoassays were employed to study variation in the concentration of corticosterone, ACTH and beta-endorphin in rat blood plasma at different times of the 30-hour immobilization and under the effect of a short-term action of ecologically significant negative stimulation emanating from other animals. Both prolonged immobilization stress and short-term emotional reaction produced appreciable alterations in the blood plasma content of all the hormones under study. The findings indicate that variations in the corticosterone and beta-endorphin levels were in the best agreement.     

Central and peripheral noradrenergic tone in primary hypertension

The contents of norepinephrine (NE), epinephrine (E), dopamine (DA), normetanephrine (NMN), and 4-hydroxy-3-methoxyphenylethylene glycol (MHPG) were measured in the plasma and cerebrospinal fluid (CSF) of 66 patients with primary hypertension and 24 patients with normal blood pressure and minor neurological disorders. Plasma and CSF NE and NMN concentrations were raised in the hypertensive patients. The plasma and CSF NE levels and arterial blood pressure of a small subset of hypertensive patients were normalized after clonidine therapy. In hypertensive patients the content of DA was lower and the ratio of NE/DA was greater; CSF and plasma NE contents were related to the level of arterial blood pressure; and the content of MHPG in CSF was linked strongly with NE content in plasma and CSF and to the level of arterial blood pressure. Thus both central sympathetic nerve tone and peripheral sympathetic nerve tone were enhanced in young patients with uncomplicated hypertension. The elevated levels of neurohormones and their metabolites in some patients with primary hypertension may be related to increased synthesis and release of neural NE and may be pathogenic in the blood pressure elevation.     

Adrenergic and dopaminergic regulation of circulating beta-endorphin-like immunoreactivity in hypertension.

The central alpha-2-adrenergic receptor agonist, clonidine (300 micrograms daily) significantly increased the plasma beta-endorphin-like immunoreactivity (beta ELI) in 12 patients with mild to moderate essential hypertension in a randomized, crossover study. A significant linear correlation between the increase in plasma beta ELI and the decrease in blood pressure (both systolic and diastolic) was found after clonidine administration. The role of the reduced central sympathetic tone, induced by alpha-2-adrenoceptor stimulation, in the elevation of circulating beta ELI can be suggested. The plasma beta ELI increased also significantly after the dopaminergic D-2 receptor agonist, bromocryptine treatment, (5 mg, daily) in 13 patients with borderline and mild essential hypertension in a randomized, crossover study. A significant drop in circulating noradrenaline and in arterial blood pressure and a significant linear correlation between the changes of plasma noradrenaline level and blood pressure was found after bromocryptine administration. There was no correlation between the rise in plasma beta ELI and the decrease in blood pressure after bromocryptine. The importance of the central sympathetic activity and not only a direct pituitary dopaminergic agonist effect on the beta-endorphin secretion can be stressed in the effect of bromocryptine on the immunoreactive beta-endorphin level.     

Hypoxia does not increase CSF or plasma beta-endorphin activity

The ability of moderate (30-50 Torr arterial PO2) and severe (less than 30 Torr arterial PO2) hypoxia to generate endogenous opioids that modulate ventilation was studied in unanesthetized goats. Ventilation and its components, arterial blood gas tensions and pH, and plasma and cerebrospinal fluid (CSF) beta-endorphin activity were measured before and after 4 h of sustained moderate or severe hypoxia. Ventilation, as expected, increased with hypoxia. There were no significant changes in either plasma or CSF beta-endorphin activity after sustained hypoxia. To rule out elaboration of endogenous opioids other than beta-endorphin after hypoxia, naloxone or saline was administered to five of the seven goats exposed to 4 h of severe hypoxia, and their ventilatory responses were compared for 30 additional min of hypoxic breathing. No significant differences in ventilation occurred in the two treatment groups during this time period. We conclude that, unlike increases in airway resistance, moderate and severe hypoxia do not cause the elaboration of endogenous opioids that modify respiratory output in unanesthetized adult goats. The apparent ability of hypoxia to cause elaboration of endogenous opioids in the neonate may represent a maturational phenomenon.     

Caffeine stimulates beta-endorphin release in blood but not in cerebrospinal fluid

Plasma beta-endorphin and prolactin profiles were obtained from groups of unstressed, adult male rats. The infusion of caffeine (20 mg/kg) via a chronic, indwelling intra-atrial cannula results in a prompt and sustained (2-2.5 h) rise In plasma beta-endorphin levels. The infusion of the opiate antagonist naloxone causes a modest (40%) decrease in plasma beta-endorphin and blunts the elevation in plasma beta-endorphin following caffeine administration. In contrast, plasma prolactin levels were unchanged following caffeine administration and were decreased by treatment with naloxone. Caffeine treatment did not effect CSF beta-endorphin levels or the release of beta-endorphin from hemipituitaries incubated in vitro.     

Modulation of the hypoglycemic effect of insulin during lateral transcerebral electrostimulation

Experiments on rabbits have studied the effect of lateral transcerebral electrical modulations with weak impulse current on hypoglycemic insulin effect. Two series of experiments were performed on 15 intact animals each. Right-sided electrical stimulation in the first series of experiments produced a trend toward a decrease in fasting blood sugar concentration. In the second series of experiments there was hypoglycemic action of a standard exogenous insulin dose. Transcerebral left-sided electrical stimulation caused no such effects. It has been concluded that the modulation of hypoglycemic exogenous insulin effect was possible due to unilateral transcerebral right-sided electrical stimulation.     

Participation of endogenous opioid peptides in the pathogenesis of motion sickness

Investigations were performed with 19 healthy male volunteers to specify a possible role of endogenous opioid peptides in the pathogenesis of motion sickness. For this purpose the test subjects were administered naloxone, a specific antagonist of opiates and opioids, before rotation and during rotation in a BU-4 armchair at a rate of 30 rpm. In addition, the content of beta-endorphin in blood plasma was measured. It was discovered that naloxone exerts both prophylactic and therapeutic effects as regards the simulated motion sickness. In this respect it was more efficacious than the reference drug scopolamine. After rotation there was a significant increase in the beta-endorphin content in the blood plasma of the test subjects. It is assumed that endogenous opioid peptides (in particular beta-endorphin) may be directly involved in the genesis of vestibulo-vegetative disorders in motion sickness.     

Effect of neonatal treatment with monosodium glutamate on vasopressin release during foot shock stress in the rat

Several lines of evidence indicate that beta-endorphin inhibits the release of vasopressin during foot shock-induced stress in the rat. This study was to evaluate the relative importance of the hypothalamic versus the pituitary pool of beta-endorphin. Neonatal treatment with monosodium glutamate (MSG) reduced drastically the content of beta-endorphin-like immunoreactivity (beta-EI) of hypothalamus but not the beta-EI concentration in the pituitary; the content of vasopressin in the hypothalamus and the pituitary was not altered by MSG treatment. MSG treatment had no effect on the plasma vasopressin response to inescapable electric foot shock stress, when compared to controls. Naloxone enhanced vasopressin release during stress both in MSG-treated rats and in controls. These results suggest that hypothalamic beta-endorphin is not involved in the control of vasopressin release during foot shock-induced stress in the rat.     

不同频率经皮穴位电刺激对妇科腹腔镜手术患者术后认知功能的影响

目的:评价不同频率经皮穴位电刺激对妇科腹腔镜手术患者术后认知功能的影响。方法:共选取择期行妇科腹腔镜手术患者80例,根据经皮穴位电刺激频率不同随机分成4组,N组患者20人不做经皮穴位电刺激,E1-E3组患者60人术中在内关、百会和风池穴使用经皮穴位电刺激,其中E1组经皮穴位电刺激频率为2Hz,E2组频率为100 Hz,E3组频率为2/100 Hz。观察四组患者术后认知功能障碍发生率之间的差异。结果:与N组比较E1-E3组POCD的发生率明显较低,差异具有统计学意义(P0.05)。但E1、E2、E3组患者POCD的发生率比较无明显差异(P0.05)。结论:经皮穴位电刺激内关、百会和风池穴可有效降低妇科腹腔镜手术患者术后认知功能障碍的发生率,但不同频率参数的刺激效果无明显差异。     

Proopiomelanocortin opioids in brain, CSF, and plasma of piglets during hypoxia

beta-Endorphin-like immunoreactivity (BELI), containing the biologically active beta-endorphin, its precursor beta-lipotropin (BLP), and deactivated product N-acetyl-beta-endorphin (ABE), were measured by radioimmunoassay in plasma, cerebrospinal fluid (CSF), and in a dorsal medullary slice containing the respiratory-related nucleus tractus solitarius (dmscNTS) of young and older piglets in normoxia and hypoxia. Significant increase with hypoxia occurred in the levels of BLP in the plasma and CSF and of BELI and ABE in the plasma of the young group. In the older group, such increases occurred in ABE levels of the dmscNTS, in BLP and ABE levels of the CSF, and in plasma BELI. Estimated levels of pure beta-endorphin were higher in the CSF of young piglets during both control and hypoxia. With hypoxia, these estimated levels increased significantly in the plasma of the young age group but showed only a borderline increase in the old group. It is possible that higher opioid levels in the CSF of young as compared with older neonates, enhanced by a greater opioid increase in their plasma during hypoxia, may help explain the suppressed respiratory response to hypoxia of the newborn.     

Analysis of the mechanism of the stress-protective action of delta sleep-inducing peptide

By RIA there were studied the contents of corticosterone, ACTH, beta-endorphin and insulin in the blood plasma, met- and leu-enkephalin in different regions of the rat brain and in the adrenal glands after a 6-hour immobilization. The stress increased the content of corticosterone, ACTH, beta-endorphin, but not insulin in the blood plasma, and the levels of met-enkephalin in the adrenal glands, but decreased the met-enkephalin contents in the striatum. The injection of DSIP (0.1 mg/kg, i/p) blocked partly the elevation of corticosterone only. The authors propose, that stress-protective action of DSIP is realized with the involvements of the hypothalamo-pituitary-adrenal gland system.     

Central alpha-activation by clonidine reduces plasma level of beta-endorphin in patients with essential hypertension

Whether peripheral beta-endorphin contributes to the antihypertensive action of clonidine was examined by measuring plasma levels of beta-endorphin-like immunoreactivity (beta EpLI) after acute administration of clonidine in patients with essential hypertension. Administration of clonidine (0.225 mg) in one dose significantly lowered blood pressure, decreased heart rate and reduced the plasma level of beta EpLI and ACTH, while the placebo had no effect on blood pressure, heart rate or plasma level of beta EpLI suggesting that peripheral beta-endorphin does not play a major role in the antihypertensive action of acute clonidine administration.     

The stimulatory effect of beta-endorphin on the plasma prolactin levels was diminished in the rats treated with 6-hydroxydopamine

Intraventicular injection of beta-endorphin (beta LPH_61^?91) in urethane anesthetized male rats led to a dose dependent increase of plasma prolactin levels. Intravenous injection of apomorphine completely abolished the stimulatory effect of beta-endorphin. Animals treated with 6-hydroxydopamine (6-OHDA) and 6-OHDA plus desmethylimipramine showed inhibition of beta-endorphin induced prolactin release. These results suggest that beta-endorphin presynaptically inhibits the activity of dopaminergic neurones, leading to the stimulation of plasma prolactin levels.     

Effect of long-term prazosin treatment on certain humoral and metabolic factors in patients with primary hypertension]

An effect of the long-term prazosin therapy on sympathetic activity, renin plasma activity and beta-endorphin and lipid blood levels was investigated in 23 patients with the primary arterial blood hypertension. Group A included 18 patients treated with prazosin, and group B - 5 patients treated with prazosin combined with propranolol. Mean daily dose of prazosin in group A was 3.0-10.0 +/- 1.3 mg in different phases of therapy whereas in group B mean daily dose of prazosin was 3.0-6.5 +/- 1.8 mg and propranolol 50-80 mg. Significant decrease in diastolic and systolic blood pressure (p < 0.01) was achieved in both groups. Additionally significant decrease in pulse rate (p < 0.01) was seen in group B. It was found that prazosin produced significant increase in plasma noradrenaline in group A and decrease in 4-hydroxy-3-methoxyglycol excretion with the urine (p < 0.05) in both groups. Moreover, negative correlation between a decrease in blood pressure (diastolic) and noradrenaline excretion with the urine (p < 0.05) was noted in group A. No effect of prazosin therapy on plasma renin activity, beta-endorphin and lipids blood levels was observed in both groups. These results suggest that prazosin therapy in patients with the primary blood hypertension exerts an effect on sympathetic activity and does not change plasma renin activity or blood beta-endorphin and lipids levels.     

Opioid peptides and immunodysfunction in patients with major depression and anxiety disorders

To assess cell-mediated immunity in depression and anxiety disorders and to elucidate whether immunodysfunction might be related to a high opioid activity, a prospective study of patients with major depression (n = 34) or anxiety disorders (n = 21) was performed. Cellular immunity tests, the in vitro effects of naloxone on monocytes, and beta-endorphin plasma levels were investigated. Peripheral blood mononuclear cells and some monocyte parameters were determined by flow cytometry. Natural killer (NK) cell activity was studied by cytotoxicity, gamma-interferon production by a standard bioassay, monocytic phagocytosis by ingestion of Candida albicans and latex, and blastogenesis by stimulation with phytohaemaglutinin. In major depression and anxiety: 1) a marked reduction in the number of monocytes that ingested particles and expressed cytoskeletal intermediate filaments and surface structures (CR1 receptors and HLA-DR antigens); 2) a monocytosis that was not able to normalize the count of functioning monocytes; 3) an in vitro correction of the monocyte dysfunction by naloxone; 4) a decrease in NK cell number and activity; and 6) an anergy to candidin and tuberculin and a diminished lectin-induced blastogenesis were observed. Some of these immune changes correlated closely with plasma beta-endorphin abnormally high in all the cases. In conclusion, a naloxone-reversible monocyte dysfunction, associated to decreased NK activity and cell-mediated hypersensitivity, was found together with high of beta-endorphin plasma levels. In addition, results suggest that these immunological alterations may be useful in the clinical management of patients with these psychiatric diseases.     

Restriction of placental growth in sheep enhances placental metabolism of fetal beta-endorphin-like immunoreactivity

The opioid polypeptide beta-endorphin is present in fetal blood but it is not clear whether its source is the fetus or the placenta. We therefore measured beta-endorphin in extracts of fetal femoral arterial and umbilical venous blood plasma in sheep by radioimmunoassay to determine whether the fetus or the placenta is the major source of beta-endorphin in the fetal circulation. Chromatographic analysis of extracts of fetal arterial plasma showed that beta-lipotropin and other precursors of beta-endorphin made only a minor contribution to the immunoreactivity detected. Concentrations of immunoreactive beta-endorphin were higher in the femoral artery than in the umbilical vein in fetal sheep between 113 and 128 days of pregnancy. Therefore the placenta removes beta-endorphin or a closely related polypeptide of fetal origin from the umbilical circulation in sheep at this stage of gestation. Acute hypoxaemia and hypoglycaemia increase the concentrations of immunoassayable beta-endorphin in blood plasma of adult and fetal sheep, but little is known about the effects of chronic hypoxaemia or hypoglycaemia on the circulating levels of beta-endorphin and related polypeptides in the fetus. Therefore we also measured immunoreactive beta-endorphin in blood plasma from fetal sheep in which growth retardation in association with restricted placental growth was produced by removal of endometrial caruncles before mating. Intra-uterine growth retardation was accompanied by chronic hypoglycaemia and chronic hypoxaemia in the fetuses. This was not associated with higher concentrations of beta-endorphin-like immunoreactivity in fetal arterial or umbilical venous plasma, but was accompanied by significantly increased placental extraction of fetal immunoreactive beta-endorphin from the umbilical circulation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of stress on calcium homeostasis in sheep

The acute effect of stress on the plasma and cerebrospinal fluid (CSF) immunoreactive parathyroid hormone (PTH) response was studied in 6 merino sheep. Stress was exerted by weak periodical electric square waves (PESW). In addition, the effect of intravenous injection of adrenaline was studied. Under stress conditions (PESW or adrenaline injection), plasma PTH increased up to 30% and up to 50%, respectively. Weak periodical electric square waves of 3-4 mA decreased CSF PTH concentrations by up to 50%. The effect of adrenaline injection on the CSF PTH was not significant. Total calcium and magnesium in plasma and CSF did not change. Our results showed that the effect of stress on the CSF PTH is opposite to the effect on plasma PTH, and suggest that both, PESW and adrenaline, affected PTH in plasma and CSF by a Ca-independent mechanism.     

Hypoinsulinemic and hyperglycemic effects of beta-endorphin in rabbits

The present study was designed to investigate the in vivo effects of beta-endorphin on plasma levels of glucagon, insulin and glucose in rabbits, and to elucidate some of the mechanisms involved. beta-Endorphin (50 micrograms) injected intravenously into fasted rabbits, decreased plasma levels of insulin (-4.5 +/- 1.3 microU/ml, P less than 0.05) and increased plasma levels of glucose (+2.7 +/- 0.4 mmol/l, P less than 0.05). Similar hypoinsulinemic and hyperglycemic effects were observed for 25 and 2.5 micrograms beta-endorphin in fasted and 50 and 0.5 micrograms beta-endorphin in fed rabbits. beta-Endorphin produced slight and transient increases in plasma levels of glucagon at the highest dose in fed rabbits, only (+80 +/- 9 pg/ml, P less than 0.05). The beta-endorphin-induced hypoinsulinemia was not inhibited by phentolamine, yohimbine, propranolol or atropine, which is in consistency with a direct inhibitory effect of beta-endorphin on the beta-cell in rabbits. The beta-endorphin-induced hyperglycemia was reduced by naloxone (+0.8 +/- 0.1 mmol/l) but not by N-methyl-naloxone (ORG 10908) a peripheral opiate receptor blocking drug (+2.2 +/- 0.2 mmol/l), suggesting a central nervous action on opiate receptors. This central action of beta-endorphin was probably not mediated by catecholamine release or other stimulation of adrenergic or muscarinic receptors, since the beta-endorphin-induced hyperglycemia was not inhibited by phentolamine, yohimbine, propranolol or atropine. These results suggest that the beta-endorphin-induced hyperglycemia was caused, at least in part, by a peripheral inhibition of insulin release and a central stimulation on glucoregulation.