Endorphin Activity Research Articles

CHARACTERIZATION OF β-ENDORPHIN ACTIVITY IN THE FETUS: ACETYLATED β-ENDORPHIN (AC β-EP) AND TOTAL β-ENDORPHIN (β-EP) DURING HYPOXIA

Hypoxia is associated with high concentrations of total plasma β-EP in both human umbilical cord and fetal lamb. To characterize this endorphin activity we used RIA to measure AC β-EP (antibody reacts <1% with β-EP) and total plasma β-EP (antibody reacts equally with β-EP and AC β-EP). 9 fetal lambs were studied before and after exposure of the pregnant ewe to 10% O2 × 30 min with and without fetal dexamethazone pretreatment. In 13 hypoxia studies (PaO2 22±1 to 12±1 mmHg), AC β-EP remained unchanged (85±11 and 109±14 pg/ml mean ±S.E.) while total β-EP increased (102±21 to 557±165 pg/ml, p<.01). Thus it is likely that inactive AC β-EP is the major endorphin species in the unstressed fetus while biologically active β-EP increases with hypoxia. In 5 hypoxia studies dexamethazone pretreatment had no effect on AC β-EP level while the increase in total β-EP was blunted (108±25 to 158±12 pg/ml). There was an inverse correlation of AC β-EP with gestational age (R=-0.49, p<.01, 113-142d, N=28). The total β-EP response to hypoxia was less before than after 130 d gestation. Thus biologically inactive AC β-EP released by the unstressed fetus in decreasing amounts toward term is unaffected by hypoxia or glucocorticoids while active β-EP release is increased by hypoxia and suppressed by glucocorticoids. Speculation: Data are consistent with diminution in tonic activity of intermediate (AC β-EP release) and enhancement of anterior β-EP release) pituitary activity with gestational maturation.

Electrodermal non-responding in schizophrenia: Relationships to attentional, clinical, biochemical, computed tomographical and genetic factors

The purpose of the present study was to examine whether a psychophysiologically delineated subgroup of electrodermally non-responding subjects show deviations in other data domains. Specifically, we examined clinical ratings of psychopathology, cognitive measures of distractibility in short-term memory, family history of schizophrenia, as well as biochemical indices of monoamine and endorphin activity, and measures derived from computed tomography. The non-responders had significantly lower skin conductance level, less spontaneous fluctuations, and a smaller ratio of elicited to spontaneous responses. The non-responders had a significantly higher incidence of schizophrenic relatives than the responders, and tended to show more psychotic symptoms. The two groups did not differ in cognitive distractibility, or in biochemical and computed tomographical measures.

Opioid activity released from cat spinal cord by sciatic nerve stimulation

Spinal superfusion was performed in anesthetized cats before and during sciatic nerve stimulation. The superfusates were fractionated on Sephadex G-10 columns and thereafter on electrophoresis and HPLC. The endorphin activity was monitored by radioreceptor and radioimmunoassays. In additional experiments, chromatographic fractions were subjected to enzymatic digestion prior to radioimmunoassay. Nerve stimulation caused a release of at least three different endorphins which separated on electrophoresis, one of which comigrated with [Met] enkephalin-Lys 6. The identity of this peptide was further supported by HPLC analysis and radioimmunoassay. Furthermore, enzymatic degradation experiments provided evidence for the presence of enkephalin sequences in all three components released by stimulation. There were also increased dynorphin concentrations during stimulation. These findings suggest that at least two different endorphin systems (enkephalin and dynorphin) are functionally present in spinal cord and may be activated by somatic stimulation.

Endorphins in the cerebrospinal fluid of psychiatric patients.

In this paper we have reported the results of studies in psychiatric patient groups using the strategy of measuring opioid activity and beta-endorphin (ir) in CSF. Our findings do not lend support to the notion of excess endorphin activity in schizophrenia, but rather suggest the possibility of a decrease in endogenous opioid activity in some schizophrenic patients. In affectively ill patients our data suggest that there may be a relative change in endogenous opioid system activity across state change in manic-depressive illness. Who also found a relationship between nurses' ratings of anxiety and CSF opioid activity in depressed patients, although it is unknown whether this directly relates to the pathophysiology of this symptom, or is related to stress response. The relationship between CSF opioid activity and HPA axis activity, as reflected by urinary free cortisol excretion, supports the notion of important physiologic relationships between these systems and raises the issue of a role for the endogenous opioid system in the abnormal activation of this system in depression. Finally, the finding of increased CSF opioid activity in anorexia nervosa patients when a minimum weight coupled with data relating endogenous opioids to eating behavior raises interesting questions regarding a possible involvement of the endogenous opioid system involvement in this illness.

Absence of naloxone sensitivity in obese humans.

Studies in rodents suggest the possibility of an association between elevated endogenous opiate activity and overeating and obesity. One measure of elevated opiate activity is sensitivity to the opiate antagonist naloxone. Seven massively obese human subjects showed no subjective or physiological sensitivity to large intravenous doses of naloxone. This finding fails to support a relationship between elevated endorphin activity and human obesity.

Beta-Endorphin immunoreactivity and acute behavioral distress in children with leukemia.

Endogenous opiates have been implicated in pain and stress experiences. In order to directly assess the relationship between endorphin activity and acute behavioral distress, beta-endorphin immunoreactivity (beta-EPI) was measured by radioimmunoassay in cerebrospinal fluid of 75 children with acute leukemia undergoing routine lumbar puncture. These data were related to four measures of behavioral distress collected during the procedure. For children 4 years of age and above, beta-EPI correlated inversely with age (r = -.31,p less than or equal to .05). All behavioral measures also inversely correlated with age (r = -.26 to -.67,p less than or equal to .05 to .001). Females had a significantly lower mean beta-EPI than males (p less than or equal to .01), and exhibited greater behavioral distress. beta-EPI and behavioral measures interacted with the use of specific antileukemia agents. L-Asparaginase was associated with lower beta-EPI (p less than or equal to .05), while prednisone was associated with lower behavioral distress on three of the four measures (p less than or equal to .05 to .01). After controlling for age, sex, and chemotherapy, beta-EPI and nurse ratings of anxiety were positively correlated (partial correlation coefficient = .31, p less than or equal to .05). Correlations between beta-EPI and other behavioral measures demonstrated positive trends. Results of this study are interpreted as support for the reactive nature of beta-EPI in cerebrospinal fluid to acute distress, and may help explain documented sex differences in distress behavior. Potential clinical implications and directions for further research are discussed.

Human lymphocyte production of corticotropin and endorphin-like substances: association with leukocyte interferon.

Human leukocyte interferon (hIFN-alpha) preparations contain immunologically and biologically recognizable endorphin and corticotropin-like (ACTH-like) activities. The ACTH bioactivity was demonstrable only after pepsin or acid treatment. Highly purified hIFN-alpha was composed of two molecular species of interferon (18,500 and 23,000 daltons). Endorphin activity was associated with both of these molecules. Pepsin treatment of the 23,000-dalton but not the 18,500-dalton hIFN-alpha generated ACTH activity. In acid, the 23,000-dalton hIFN-alpha broke down into the 18,500-dalton form and ACTH (4500 daltons). The ACTH derived from hIFN-alpha by pepsin digestion comigrated with a purified ACTH standard in NaDodSO4/polyacrylamide gel electrophoresis. hIFN-alpha-producing lymphocytes showed positive immunofluorescence after staining with highly specific antisera to ACTH alpha-(1-13) and gamma-endorphin. Essentially 100% of the human peripheral lymphocytes were capable of producing both ACTH and gamma-endorphin-related substances, presumably associated with hIFN-alpha. These results strongly suggest a circuit between the immune and neuroendocrine systems which involves neuroendocrine hormone-like substances, some of which are associated with hIFN-alpha

Relationships between CSF levels of endorphins and monoamine metabolites in chronic pain patients.

This paper is one in a series, which attempts to introduce objective psychophysical and biochemical criteria for the characterization and diagnosis of chronic pain syndromes. Experimental and clinical work suggest that serotonin and endorphins are important in the sensation and expression of pain. The levels of 5-hydroxy indole acetic acid (5 HIAA), homovanillic acid (HVA) and endorphin Fraction I in the cerebrospinal fluid were therefore measured in a series of 40 patients with chronic pain. The levels of all measured variables were lower than normal in patients with pain of mainly organic origin (n=22), while patients with mainly psychogenic pain (n=18) had high levels. However, only the difference in Fraction I levels between the two categories of patients reached statistical significance. There was also a statistically significant positive correlation between 5 HIAA and Fraction I levels (in the total group, and organic pain subgroup), but the corresponding correlation between HVA and Fraction I did not reach a statistically significant level. Patients were also divided into two groups with high (n=23) and low (n=17) 5 HIAA content, respectively, according to Asberg et al. (1976). There was a highly significant difference also in Fraction I and HVA between the two groups. The results strongly suggest an intimate relationship between 5 HT, to a lesser extent dopamine, and endorphin activity in pain perception and the reaction to pain in these patients.

Endorphins in brains of decapitated and microwave-killed mice

The size distribution of opioid peptides (endorphins) in mouse brain was determined by gel filtration, using the inhibition of stereospecific 3H-etorphine binding to guinea pig brain membranes as a measure of endorphin activity. The largest endorphin was about the same size as β-LPH-(61–91), the next largest was about half this size and the smallest was the size of the pentapeptide enkephalins. There was no important difference in the size distribution between brains of mice killed by rapid microwave irradiation and those killed by decapitation. Thus, opioid peptides of all three size classes appear to be present in the brain in vivo .

Lipotropin: Localization by radioimmunoassay of endorphin precursor in pituitary and brain

Beta-Lipotropic Hormone (LPH) was estimated in pituitary and brain by a radioimmunoassay specific for the N-terminal, non-opiate portion of the protein, and endorphin activity by an opiate radioreceptor assay. The intermediate pituitary is most concentrated in LPH and endorphin. Gel filtration indicated the presence in the pituitary of intact LPH and N-terminal fragments but only intact LPH in brain. Endorphin activity in pituitary is associated primarily with a component of 3000 daltons and to a lesser extent with one of about 2000 daltons. Brain endorphin activity is mostly accounted for by a 2000 dalton component, enkephalins representing an apparently minor activity. In pituitary and brain LPH and endorphin are entirely associated with a 12,000 g/10 min fraction.

Opioid peptides (endorphins) in pituitary and brain

(1) There are at least three types of endorphin in pituitary and brain. (2) β-lipotropin (βLPH) is a prohormone for one type. All fragments of the type β-LPH-(61-n) are approximately equipotent in the myenteric plexus bioassay. Met-enkephalin [β-LPH-(61–65)] is of this type. In the bioassay and in the receptor binding assay, these peptides are somewhat less potent than morphine. (3) The second type appears to have about the same molecular weight as β-LPH-(61–91). Endorphins of this type are more potent, and their activity is destroyed readily by trypsin. Like the β-LPH type, their opioid activity is destroyed by cyanogen bromide (i.e. they have a critically placed Met residue). Much of the endorphin activity of porcine pituitary is of this type. (4) The third type also has about the same molecular weight as β-LPH-(61–91), but exists as well in a smaller form (1200–1400 daltons). The opioid activity of these endorphins is destroyed by trypsin; but it is insensitive to cyanogen bromide and therefore the peptide could possibly contain Leu-enkephalin. These endorphins are found in beef brain and pars nervosa of beef pituitary. (5) Endorphin activity in beef and rat brain has been found associated with peptides of about the same molecular weight as the native endorphins in pituitary (approx 3000 daltons) as well as in smaller peptides.

Endorphin activity in anterior, intermediate, and posterior pituitary

The content of endogenous morphine-like substance in bovine pituitary and brain was determined by an opiate radioreceptor assay. The intermediate lobe was most concentrated in activity and the brain least concentrated. Most of the endorphin is obtained in a 120 000 g-min fraction from pituitary or brain homogenates.