Degradation of [3H]β-endorphin in rat plasma is increased with chronic stress

doi:10.1016/0014-2999(89)90583-9

European Journal of Pharmacology

Volume 167, Issue 2, 22 August 1989, Pages 229-236

https://doi.org/10.1016/0014-2999(89)90583-9 Get rights and content

Abstract

With a number of acute stressors β-endorphin is released into plasma. It is unclear if β-endorphin is converted into any other biologically active products, nor it is clear if the rate or pathways of degradation are changed during chronic stress. To explore these issues, we incubated [³H]β-endorphin_h labeled in positions 1 and 27 with plasma from normal and chronically footshocked rats and measured the rate of conversion of the label from β-endorphin size material to smaller size material. Initial separations were done using a G-50 molecular sieving column, with subsequent characterization and identification on HPLC. By G-50 sieving, there is a time dependent formation of only one radioactive peak. HPLC identification demonstrates γ-endorphin and another unidentified peak. This enzymatic activity is increased in the plasma of chronically stressed rats.

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It seems possible therefore that saliva neuropeptides are transported into the bloodstream, contributing to the formation of the very large pool of plasma informational peptides. In such a context, the role of behavioural factors in controlling the release of these peptides by the salivary glands may be similar to that reported for other substances, such as monoamine oxidase in the central nervous system (Lemoineet al., 1990), secretion of proteases by mast cells (MacQueen et al., 1989), or enzyme degradation of opioid peptides in plasma (Young et al., 1989; Babst et al., 1999). As is known for other neuropeptides, some of the above-mentioned effects are regulated by enzyme degradation.
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It seems therefore possible to suppose that even locally secreted neuropeptides can be transported into the bloodstream, contributing to the very large pool of plasma informational peptides. In such a context, the role of behavioral factors in controlling the active concentration of saliva neuropeptides may be similar to that reported in the case of other substances, such as MAO in the central nervous system [30], secretion of proteases by mast cells [37], plasma degradation of opioid peptides [5,56], or in neuroimmune interactions (e.g. 2). The presence of diverse enzyme classes has been described in saliva: among these, protein kinases are reported by Nam et al. [40], and renin by several authors [6,10,38].
The possible presence of enzymes able to hydrolyze leucine enkephalin has been investigated in human saliva. The data obtained indicate that, in the presence of saliva, Leu-enkephalin is partially hydrolyzed. The disappearance of the substrate is paired with the formation of hydrolysis byproducts whose composition indicates the presence of all three classes of enzymes known to hydrolyze enkephalins: aminopeptidases, dipeptidylaminopeptidases, and dipeptidylcarboxypeptidases. The presence of low molecular weight substances with inhibitory activity on proteolytic enzymes has also been detected. These substances are active on all three classes of enkephalin-degrading enzymes, although the inhibition is more evident on dipeptidylpeptidases than on aminopeptidases. Substrate degradation was found to be higher in male than in female saliva: this seems to be caused by the activities both of enzymes and low molecular weight inhibitors that are different in the two sexes.
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The enzyme hydrolysis of labelled leu-enkephalin in the presence of plasma enzymes was studied by kinetic and chromatographic techniques in a group of allergopathic patients in the acute and quiescent stage; data obtained have been compared with those obtained with normal controls. Results shown indicate that in the quiescent stage substrate degradation is reduced, and that the pattern of the hydrolysis by-products is modified with respect to the controls. In the acute as compared to the quiescent stage, enkephalin hydrolysis is further reduced, and the pattern of hydrolysis by-products is further modified. ANOVA analysis of these data indicates that the dependency of hydrolysis reduction upon the grouping of subjects (i.e., controls, quiescent and acute stage) is statistically very significant. Reduced substrate hydrolysis, and modified hydrolysis pattern, appears to be associated with decreased activity of the enzymes involved and more significantly with increased activity of the low molecular weight plasma inhibitors. The combination of these two factors appears to define a hydrolysis pattern characteristic of the allergopathic subjects, similar in the quiescent and acute phase, and different from that observed in the controls.

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Degradation of [3H]β-endorphin in rat plasma is increased with chronic stress

Abstract

J. Biol. Chem.

Biochem. Biophys. Res. Commun.

Peptides

Biochem. Biophys. Res. Commun.

Arch. Biochem. Biophys.

Neuropeptides

Anal. Biochem.

Biochem. Biophys. Res. Commun.

Biochem. Biophys. Res. Commun.

J. Biol. Chem.

Life Sci.

Brain Res.

Psychoneuroendocrinology

Peptides

Studies on limited proteolysis and degradation of lipotropin C-fragment

Biochem. Soc. Trans.

γ-Endorphin, α-endorphin and met-enkephalin are formed extracellularly from lipotropin C fragment

Nature

Selective conversion of β-endorphin into peptides related to γ- and α-endorphin

Nature

Human plasma β-endorphin-like peptides: A rapid, high recovery extraction technique and validation of the radioimmunoassay

J. Clin. Endocrinol. Metab.

N-Acetyl-γ-endorphin in rat spermatogonia and primary spermatocytes

J. Clin. Invest.

Biosynthesis of β-endorphin from β-lipotropin and a larger molecular weight precursor in rat pars intermedia

Psychopathology as a neuropeptide function

Degradation of [³H]β-endorphin in rat plasma is increased with chronic stress