β-Endorphin stimulates human polymorphonuclear leukocyte superoxide production via a stereoselective opiate receptor

Burt Sharp, D. T. Tsukayama, G. Gekker, W. F. Keane, P. K. Peterson

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

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 β-endorphin (β-END). β-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 β-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 β-END can apparently bind to and activate cellular functions by nonopiate receptors, N-acetyl-β-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 β-END whereas (+)-naloxone was entirely ineffective. At 10-8 M both stereoisomers also failed to inhibit formyl-methione-leucine-phenylalanine 10-8 M. Thus, at the picomolar concentration present in the human systemic circulation, β-END activates oxygen metabolism by polymorphonuclear leukocytes through stereoselective, naloxone-sensitive opiate receptors.

Original languageEnglish (US)
Pages (from-to)579-582
Number of pages4
JournalJournal of Pharmacology and Experimental Therapeutics
Volume242
Issue number2
StatePublished - 1987

Fingerprint

Endorphins
Opioid Receptors
Naloxone
Superoxides
Neutrophils
Phenylalanine
Leucine
Phenolsulfonphthalein
Peptides
Stereoisomerism
Opioid Peptides
Nitroprusside
Horseradish Peroxidase
Methionine
Catalase
Hydrogen Peroxide
Oxygen
Enzymes

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

β-Endorphin stimulates human polymorphonuclear leukocyte superoxide production via a stereoselective opiate receptor. / Sharp, Burt; Tsukayama, D. T.; Gekker, G.; Keane, W. F.; Peterson, P. K.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 242, No. 2, 1987, p. 579-582.

Research output: Contribution to journalArticle

@article{04c64d7ee9df49e5be56a651102c9dfa,
title = "β-Endorphin stimulates human polymorphonuclear leukocyte superoxide production via a stereoselective opiate receptor",
abstract = "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 β-endorphin (β-END). β-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 β-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 β-END can apparently bind to and activate cellular functions by nonopiate receptors, N-acetyl-β-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 β-END whereas (+)-naloxone was entirely ineffective. At 10-8 M both stereoisomers also failed to inhibit formyl-methione-leucine-phenylalanine 10-8 M. Thus, at the picomolar concentration present in the human systemic circulation, β-END activates oxygen metabolism by polymorphonuclear leukocytes through stereoselective, naloxone-sensitive opiate receptors.",
author = "Burt Sharp and Tsukayama, {D. T.} and G. Gekker and Keane, {W. F.} and Peterson, {P. K.}",
year = "1987",
language = "English (US)",
volume = "242",
pages = "579--582",
journal = "Journal of Pharmacology and Experimental Therapeutics",
issn = "0022-3565",
publisher = "American Society for Pharmacology and Experimental Therapeutics",
number = "2",

}

TY - JOUR

T1 - β-Endorphin stimulates human polymorphonuclear leukocyte superoxide production via a stereoselective opiate receptor

AU - Sharp, Burt

AU - Tsukayama, D. T.

AU - Gekker, G.

AU - Keane, W. F.

AU - Peterson, P. K.

PY - 1987

Y1 - 1987

N2 - 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 β-endorphin (β-END). β-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 β-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 β-END can apparently bind to and activate cellular functions by nonopiate receptors, N-acetyl-β-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 β-END whereas (+)-naloxone was entirely ineffective. At 10-8 M both stereoisomers also failed to inhibit formyl-methione-leucine-phenylalanine 10-8 M. Thus, at the picomolar concentration present in the human systemic circulation, β-END activates oxygen metabolism by polymorphonuclear leukocytes through stereoselective, naloxone-sensitive opiate receptors.

AB - 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 β-endorphin (β-END). β-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 β-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 β-END can apparently bind to and activate cellular functions by nonopiate receptors, N-acetyl-β-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 β-END whereas (+)-naloxone was entirely ineffective. At 10-8 M both stereoisomers also failed to inhibit formyl-methione-leucine-phenylalanine 10-8 M. Thus, at the picomolar concentration present in the human systemic circulation, β-END activates oxygen metabolism by polymorphonuclear leukocytes through stereoselective, naloxone-sensitive opiate receptors.

UR - http://www.scopus.com/inward/record.url?scp=0023199937&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0023199937&partnerID=8YFLogxK

M3 - Article

VL - 242

SP - 579

EP - 582

JO - Journal of Pharmacology and Experimental Therapeutics

JF - Journal of Pharmacology and Experimental Therapeutics

SN - 0022-3565

IS - 2

ER -