Beta-endorphin stimulates human polymorphonuclear leukocyte superoxide production via a stereoselective opiate receptor.
Opioid peptides have been shown to modulate the function of cells associated with host defense. Both opiate and nonopiate receptor mechanisms have been shown to mediate cell responses to these peptides. In this study we used a ferricytochrome C reduction microassay to measure superoxide (O2-) production by human polymorphonuclear leukocytes after stimulation with beta-endorphin (beta-END). beta-END was found to stimulate O2- release at concentrations from 10(-14) to 10(-8) M; the peak response occurred at 10(-12) M. A microassay based on the horseradish peroxidase-mediated oxidation of phenol red was used to demonstrate the production of hydrogen peroxide H2O2, by beta-END at 10(-12) M. The accumulation of H2O2 was reduced by the inhibitor, nitroprusside, and by the converting enzyme, catalase. The accumulation of O2- in response to the potent chemotactic peptide formyl-methionine-leucine-phenylalanine was studied and a distinctly different dose-response profile with a peak response at 10(-8) M was observed. Because beta-END can apparently bind to and activate cellular functions by nonopiate receptors, N-acetyl-beta-END was tested. At doses between 10(-14) and 10(-8) M, it failed to effect O2- accumulation. Moreover, (-)-naloxone 10(-12) M was shown to completely abolish the stimulatory effect of equimolar beta-END whereas (+)-naloxone was entirely ineffective. At 10(-8) M both stereoisomers also failed to inhibit formyl-methionine-leucine-phenylalanine 10(-8) M. Thus, at the picomolar concentration present in the human systemic circulation, beta-END activates oxygen metabolism by polymorphonuclear leukocytes through stereoselective, naloxone-sensitive opiate receptors.
D004723:Endorphins / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000096:biosynthesis; D009270:Naloxone / Q000494:pharmacology; D009504:Neutrophils / Q000378:metabolism*; D011957:Receptors, Opioid / Q000502:physiology*; D013268:Stimulation, Chemical; D013481:Superoxides / Q000096:biosynthesis*; D001615:beta-Endorphin
D004723:Endorphins; D011957:Receptors, Opioid; D013481:Superoxides; D009270:Naloxone; D001615:beta-Endorphin; D006861:Hydrogen Peroxide