Plasma Beta-endorphin Levels Research Articles

The role of endogenous opioids in congestive heart failure: effects of nalmefene on systemic and regional hemodynamics in dogs.

We studied the role of endogenous opiates and their interrelationships with the sympathetic nervous system in an experimental preparation of right-sided congestive heart failure (CHF) produced by surgical tricuspid avulsion and progressive pulmonary arterial constriction. Three groups of dogs with CHF and one group of sham-operated dogs were studied. One group of dogs with CHF was given normal saline as pretreatment, while the other two groups were pretreated with either propranolol alone (beta-blockade) or propranolol plus prazosin (alpha- plus beta-blockade). CHF was characterized by weight gain, ascites, elevated right atrial pressure, tachycardia, and reduced cardiac output. Compared with sham-operated animals, animals with CHF exhibited significantly higher baseline levels of plasma beta-endorphin and cortisol. Furthermore, only the animals with CHF responded to the opiate receptor-antagonist nalmefene with significant increases in plasma beta-endorphin, cortisol, and adrenocorticotropic hormone. Administration of nalmefene increased aortic blood pressure, cardiac output, left ventricular dP/dt and dP/dt/P, and blood flow to the myocardium, skeletal muscle, and kidneys in dogs with CHF, but had no appreciable effects in sham-operated dogs. beta-Receptor blockade abolished the increase in cardiac output, left ventricular performance, and blood flow produced by nalmefene, but had no effect on the pressor response to nalmefene. The increase in mean aortic pressure in the beta-blockade group was accompanied by an increase in skeletal muscle vascular resistance. Addition of prazosin in the alpha- plus beta-blockade group abolished the increases in mean aortic pressure and skeletal muscle vascular resistance, suggesting that the changes after propranolol probably resulted from unmasking of alpha-receptor-mediated vasoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)

Naloxone, fentanyl, and diazepam modify plasma beta-endorphin levels during surgery : Hargreaves KM, Dionne RA, Mueller GP, et al. Clin Pharmacol Ther 40:165, 1986

Naloxone, fentanyl, and diazepam modify plasma beta-endorphin levels during surgery : Hargreaves KM, Dionne RA, Mueller GP, et al. Clin Pharmacol Ther 40:165, 1986

Neuroendocrine changes in patients undergoing whole body hyperthermia.

A phase I study of whole body hyperthermia (WBH) (52 treatments/12 patients) utilizing a radiant heat device has been completed. This study incorporated a temperature escalation scheme from 39.5 to 41.8 degrees C for up to 150 min. Pain relief or a sense of well being was observed post-WBH in the first three patients entered in this study. We postulated that WBH might result in increases in the opiate peptide beta-endorphin. Therefore we elected to study prospectively the next six patients entered in this study to test the hypothesis that WBH stimulates the neuroendocrine axis. Results are reported which show thermal-induced increases in plasma levels of beta-endorphin as well as prolactin, ACTH and cortisol.

Paraventricular Lesions Abolish the Stress-Induced Rise in Pituitary Cyclic Adenosine Monophosphate and Attenuate the Increases in Plasma Levels of Proopiomelanocortin-Derived Peptides and Prolactin

Acute exposure to footshock stress increased the pituitary level of cyclic adenosine monophosphate (AMP) in vivo and sharply increased plasma levels of adrenocorticotropic hormone, beta-endorphin and beta-lipotrophic hormone, as well as prolactin. Seven days after bilateral lesions of the paraventricular nucleus of the hypothalamus, the pituitary cyclic AMP response to stress was totally eliminated and the increases in plasma levels of these pituitary hormones were blunted. We conclude that while the pituitary hormonal responses to stress might be mediated by several neurohumoral factors, the stress-induced increases in pituitary levels of cyclic AMP in vivo are mediated largely via corticotropin-releasing factor, released from neurons which project from the paraventricular nucleus to the median eminence.

Prostaglandin-Induced Mid-Pregnancy Abortion Increases Plasma and Amniotic Fluid Levels of β-Lipotropin and β-Endorphin

The continuous and progressive rise of beta-endorphin (B-EP), beta-lipotropin (B-LPH) and cortisol plasma levels during labor in term-pregnant women represents one of the most relevant maternal hormonal responses to the stress of parturition. The aim of the present study was to evaluate the changes of these hormones, both in plasma and amniotic fluid (except cortisol), in a group of pregnant women undergoing prostaglandin-induced therapeutic abortion at the 2nd trimester of pregnancy. B-EP, B-LPH and cortisol were measured by radioimmunoassay. Both plasma and amniotic fluid samples were purified through extraction and chromatography (Sephadex G-75 columns). The prostaglandin derivative, 16-phenoxy-PGE2-methylsulfonylamide (sulprostone, Schering, Berlin) (500 micrograms, i.m., every 4 h), caused a rapid and significant rise of plasma B-EP, B-LPH and cortisol levels in all subjects. The relative increase of the 3 hormones was less relevant after the 2nd and absent after the 3rd injection of PGE2. The amniotic fluid concentrations of B-EP and B-LPH were also raised 2 h after the 1st injection. These data indicate that sulprostone-induced abortion activates both maternal and fetoplacental release of opioids independently of the trend of uterine contractions. The pattern of pro-opiomelanocortin-related labor differs from spontaneous labor and can probably be linked to a direct effect of the drug.

Variations in plasma beta-endorphin and cortisol levels in acutely burned children

Variations in plasma beta-endorphin and cortisol levels in acutely burned children

Fetal beta-endorphin levels in response to reductions in uterine blood flow.

Fetal beta-endorphin release has been associated with fetal hypoxia. The purpose of this study was to assess the degree of uterine blood flow reduction needed to elicit fetal beta-endorphin release in the sheep since there is a large reserve of oxygen supply to the fetus. Uterine blood flow was reduced by 26 +/- 2, 46 +/- 3 and 66 +/- 2%, producing fetal oxygen content concentrations of 5.7 +/- 0.6, 4.4 +/- 0.7 and 2.6 +/- 0.3 ml/dl, respectively. Although fetal oxygen concentrations were significantly decreased in the groups with a reduction in uterine blood flow of 46 and 66%, beta-endorphin was elevated only in the latter group. It is speculated that fetal beta-endorphin is released at a level of hypoxia which leads to a decrease in fetal oxygen consumption. A reduction in uterine blood flow of 66% appears to produce a stressful environment for the fetus as measured by fetal plasma beta-endorphin levels.

Gastric and autonomic responses to stress in functional dyspepsia.

It has been suggested that functional dyspepsia might arise from the effect of stress on upper gut motility in susceptible individuals. The aim of this study was to evaluate posticibal antral motility in the presence and absence of sustained experimental stress by means of a transcutaneous electrical nerve stimulator. Two groups of patients could be recognized from these studies: first, those with postcibal antral hypomotility that was not changed during stress; and second, patients with normal postcibal motility which was normally suppressed by stress. Experimental stress significantly increased skin conductance and plasma beta-endorphin levels. However, in these two groups, there were no differences in clinical presentation and personality traits or in autonomic and humoral variables either before or during stress. Stepwise discriminant analysis of the autonomic or humoral responses to stress was unable to predict the different postcibal antral motor responses among the subsets of patients with functional dyspepsia. These data suggest that there are two subtypes of antral motility in functional dyspepsia: disordered gastric function under basal conditions resulting in antral hypomotility, and normal basal antral motility and autonomic and gastric motor responses to stress. In the latter subgroup, the cause of symptoms is unclear, but it appears not to be a motility disorder.

Plasma beta endorphin immunoreactivity: Effects of sustained hyperglycemia with and without prior exercise

Seven healthy untrained men were studied to determine if sustained hyperglycemia is a stimulus to enhanced plasma levels of beta endorphin (β-EP) and if so whether prior exercise affects that enhancement. After an overnight fast hyperglycemia glucose clamps were performed on 3 separate days: after prior rest, 2 h after exercise, and 48 h after exercise. Subjects exercised on a bicycle ergometer for 1 h at 150 W (64% VO 2 max). Plasma glucose concentration was elevated in 4 continuous sequential stages to 7, 11, 20 and 35 mM with each stage lasting 90 min. Plasma glucose concentrations did not differ for each subject across the three clamps. β-EP immunoreactivity was measured in arterialized venous blood samples using a specific and sensitive radioimmunoassay. Resting β-EP at basal glucose concentrations was 3.8±0.7 fmol·ml −1 (mean ± se) and prior exercise either 2h (3.2± 0.5 fmol·ml −1) or 48 h (4.3± 0.7 fmol·ml −1) before a clamp study did not effect these levels, (p > 0.05). At no time during the 3 hyperglycemic clamps did plasma levels of β-EP differ significantly from resting values. At the highest level of hyperglycemia (35 mM) β-EP was 3.1±0.2, 4.9±0.6 and 4.8±0.7 fmol·ml −1 in the resting, 2h and 48 h post exercise clamp studies respectively. The significance of these data is that this lack of a response is in distinct contrast to elevations of this peptide found during hypoglycemic states. We conclude that sustained hyperglycemia is not a stimulus to enhanced secretion of β-EP into plasma and this lack of a response is not effected by prior exercise.

Effects of L-5HTP with and without carbidopa on plasma beta-endorphin and pain perception: possible implications in migraine prophylaxis.

L-Tryptophan (L-TP) has been used in migraine and other pain conditions. The mechanism underlying the analgesic effect is still partly undefined. In this study the effects of subchronic administration of L-5-hydroxytryptophan (L-5HTP) (with and without carbidopa) on plasma beta-endorphin (beta-EP) levels and subjective pain threshold and tolerance were investigated in seven healthy volunteers. To measure also an objective indicator of pain, the nociceptive flexion reflex threshold was studied. L-5HTP treatment with and without carbidopa administration increased beta-EP levels significantly (p less than 0.05). L-5HTP plus carbidopa induced an increase in beta-EP significantly (p less than 0.05) greater than that induced by L-5HTP alone. Neither the subjective pain threshold and tolerance nor the RIII threshold was modified by either treatment. Our data seem to point to the existence of a complex linkage between plasma opioid levels and pain perception.

Naloxone, fentanyl, and diazepam modify plasma beta-endorphin levels during surgery

Forty-eight patients received either naloxone (10 mg), fentanyl (0.1 mg), diazepam (0.3 mg/kg), or saline solution placebo, and then underwent surgical removal of impacted third molars under local anesthesia. Placebo resulted in significantly elevated levels of immunoreactive beta-endorphin (i beta-END), norepinephrine, and anxiety during surgery. Patients receiving naloxone had significantly greater intraoperative i beta-END and pain as compared with those receiving placebo. The naloxone effect on intraoperative pain was a result of a difference in perceived unpleasantness. Both the fentanyl and diazepam groups had significantly lower intraoperative i beta-END and anxiety levels as compared with the placebo group. Norepinephrine levels increased significantly in response to surgical stress in all groups except the diazepam group. Postoperative circulating levels of i beta-END and norepinephrine and pain increased significantly from the 1 to 3-hour postoperative period for all groups, with the exception of stable norepinephrine levels observed in patients receiving diazepam. Results indicate that opiate antagonists stimulate and agonists suppress the release of i beta-END, possibly by affecting the patient's perceived level of pain and anxiety. In addition, the association of intraoperative hyperalgesia with naloxone predosing suggests that endogenous opioid peptides inhibit the perception of intraoperative pain even in the presence of concurrent local anesthesia.

Dose-related effects of synthetic human beta-endorphin and naloxone on fed gastrointestinal motility.

In humans, plasma beta-endorphin levels rise during application of acute stressful stimuli (vertigo, cold pain, and transcutaneous electrical stimulation) that induce gut motor disturbances. Whereas it is possible that circulating beta-endorphin participates in the mediation of these central effects on gut motility, its role cannot be established solely on the basis of changes in plasma levels. Therefore, we designed the present study to investigate 1) the dose-related effects of intravenous synthetic human beta-endorphin and naloxone on gastrointestinal pressure activity in fed healthy individuals; and 2) the interactions of the opiate agonist and antagonist. Infusion of beta-endorphin increased pyloric phasic pressure activity (P less than 0.001) and induced intestinal bursts of rhythmic activity (P less than 0.05) which interrupted normal fed motility. These effects were dose related, with the pyloric dose-response profile being essentially linear. The effects in the proximal intestine were obtained with doses of beta-endorphin at 250 ng X kg-1 X min-1 or greater. In the antrum, there was an overall reduction in phasic pressure activity (P less than 0.02), which was predominantly an effect of the highest dose of beta-endorphin infused (2,500 ng X kg-1 X min-1). Naloxone by itself had no significant effect on fed upper gut motility. However, naloxone significantly inhibited the effect of the lower doses of beta-endorphin on the pylorus. In addition, naloxone significantly reduced the probability of beta-endorphin, triggering intestinal bursts of rhythmic activity. These data suggest that beta-endorphin may play a humoral role in the stimulation of fed pyloric contraction at physiological levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Hemorrhagic hypotension increases plasma beta-endorphin concentrations in the nonhuman primate.

The role which beta-endorphin plays in the pathogenesis of hemorrhagic hypotension is controversial. In the present experiment, 20 ml/kg of blood was bled from ten healthy male baboons (Papio anubis) over 60 min and then retransfused over the next 30 min. We found that the mean plasma beta-endorphin level increased 109% above baseline (p less than .05) within 15 min after starting hemorrhage, and rapidly returned to a baseline concentration with retransfusion. We conclude that in a primate species, circulating endogenous opioid peptide concentrations increase rapidly in response to sublethal hemorrhagic hypotension and normalize with restoration of the baseline intravascular volume. These findings support the concept that endogenous opioid peptides may mediate the hypotension of shock states.

PLASMA BETA ENDORPHIN IMMUNOREACTIVITY

Farrell, P. A. FACSM; Mikines, K. J.; Bach, F. W.; Sonne, B.; Galbo, H. Author Information

Beta-Endorphin/beta-lipotropin immunoreactivity in endogenous depression. Effect of dexamethasone.

This study addresses the question of whether pituitary peptides (ie, beta-endorphin) show regulatory disruption in endogenous depression and, if so, does it co-occur in the same subjects who show cortisol dysregulation. Endogenously depressed patients and psychiatric controls from three centers were evaluated, when not taking medications, and studied for plasma cortisol and beta-endorphin levels. Plasma samples were taken at four time points over one hour, on the basal day, and 16 hours after 1 mg of dexamethasone. From 33% to 69% of the endogenous patients were abnormal in their postdexamethasone cortisol levels, and from 50% to 69% were abnormal on postdexamethasone beta-endorphin values (vs 0% and 8%, respectively, for controls). When endogenous subjects were evaluated for abnormality on both cortisol and beta-endorphin, after dexamethasone, it was found that the two measures of hypothalamic-pituitary-adrenal dysfunction did not necessarily co-vary. In fact when having either abnormal beta-endorphin or cortisol levels (or both) was used as a biological marker a larger number of the endogenous patients were detected than with either measure alone. Our conclusions are as follows: Plasma beta-endorphin shows a circadian rhythm similar to that seen with corticotropin (ACTH) and is suppressable by dexamethasone. In many endogenous patients plasma beta-endorphin levels escape from dexamethasone suppression. Many of these subjects are not cortisol escapers. When abnormality of either the beta-endorphin or cortisol is considered it is clear that both levels of the hypothalamic-pituitary-adrenal axis can be dysregulated in endogenous depression.

A clinical study on the relationship between the pineal gland and the opioid system.

Recent reports point to a link between the pineal gland and the opioid system. In order to investigate this relationship, two separate studies were performed on humans. Beta-endorphin plasma levels were determined after melatonin administration (0.2 mg/kg b.w. i.m. at 2 p.m.). Melatonin serum values were evaluated after administration of FK 33-824, a met-enkephalin analogue (0.3 mg i.v. infusion at 9 a.m.). A significant decrease of beta-endorphin plasma levels was observed 120 minutes after melatonin injection. Melatonin release was stimulated by FK 33-824, with a peak at 30 minutes. The present results provide evidence of the inhibitory effect of melatonin on beta-endorphin secretion and the stimulatory action of the opioid peptides on the pineal gland. However, further studies will be required to clarify the relationship between the opioid system and the pineal gland.

Plasma β-endorphin levels in anovulatory states: changes after treatments for the induction of ovulation

The goal of this study was to evaluate the effects of menstrual cyclicity on plasma beta-endorphin (beta-EP) levels. For this purpose, beta-EP and cortisol plasma concentrations were measured during the menstrual cycle in healthy control subjects (n = 12), in patients affected by anovulatory syndrome (n = 6), and in amenorrheic patients (n = 8). In the same patients, beta-EP and cortisol were also measured under treatment for the induction of ovulation with pulsatile luteinizing hormone-releasing hormone or human menopausal gonadotropin plus human chorionic gonadotropin administration. In spontaneous and pharmacologically induced ovulatory cycles, a significant preovulatory rise of plasma beta-EP levels was always evident. Constant levels were found in the other periods of ovulatory cycles and in the patients affected by anovulatory syndrome and primary amenorrhea. Cortisol levels did not show any significant change throughout the cycle, either in controls or in patients before or after treatment. This result suggests that when ovulation occurs, plasma beta-EP levels show a relevant rise, the physiologic significance of which remains to be elucidated.

Plasma endorphins in Rett syndrome: preliminary data.

Plasma levels of beta-endorphin (beta-EP) and prolactin (PRL) were measured in 5 girls with Rett syndrome and in a control group before and after giving 10 mg metoclopramide i.v. beta-lipotropin (beta-LPH) was only measured in basal conditions. Basal values of beta-EP and beta-LPH were lower than in control individuals. The responses of plasma beta-EP to metoclopramide in Rett syndrome patients were less intense than in control individuals, while the PRL increase in girls with Rett syndrome was significantly higher than in control subjects. These preliminary data suggest a derangement of the dopaminergic system.

Diurnal Rhythms of Plasma Cortisol, Beta-Endorphin and Prolactin, and Cerebrospinal Fluid Amine Metabolite Levels before Suicide

There are indications to suggest a relationship between low levels of 5-hydroxy-indoleacetic acid (5HIAA) in the cerebrospinal fluid and suicidal behavior. Many depressed patients show an elevated cortisol secretion. As beta-endorphin is derived from the same precursor as ACTH, it is expected that plasma beta-endorphin levels will also rise in depressed patients. We report here a case of severe depression with diurnal variation who showed low CSF 5HIAA prior to his suicide. In contrast, his catecholamine metabolites were 50% above the mean values of other depressed patients. Hormonal measurements, however, showed low cortisol, prolactin and beta-endorphin levels.

Dermorphin reduces the metyrapone-evoked release of adrenocorticotropin, beta-endorphin, and beta-lipotropin in man.

The aim of this study was to investigate further the influence of dermorphin (D), a new potent opioid peptide (H-Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2), on the functional activity of the pituitary-adrenocortical system in man. Six normal men were treated with oral metyrapone to stimulate the secretion of ACTH, beta-lipotropin, and beta-endorphin. In these subjects, significant suppression of metyrapone-evoked release of ACTH and related peptides occurred during D infusion (5.5 micrograms/kg X min for 30 min) compared with that during saline infusion. These results indicate that D can induce a significant decline in plasma levels of ACTH, beta-lipotropin, and beta-endorphin, the major circulating peptides from the C-terminal part of proopiocortin, and suggest that opioid peptides may be involved in the control of the functional activity of pituitary-adrenocortical activity in man.