Ontogeny of the opioid growth factor, [Met5]-enkephalin, and its binding activity in the rat retina

1995 ◽  
Vol 12 (5) ◽  
pp. 939-950 ◽  
Author(s):  
Tomoki Isayama ◽  
W. Jeffrey Hurst ◽  
Patricia J. McLaughlin ◽  
Ian S. Zagon
Keyword(s):  
Growth Factor ◽  
Dna Synthesis ◽  
High Performance ◽  
Opioid Peptide ◽  
Binding Activity ◽  
Endogenous Opioid ◽  
Endogenous Opioid Peptide ◽  
Rat Retina ◽  
Opioid Growth Factor

AbstractThe endogenous opioid peptide [Met5]-enkephalin is a tonically active opioid growth factor (OGF) with an inhibitory action on DNA synthesis in the developing rat retina. In this study, the ontogeny of the spatial and temporal expression of OGF and its binding activity was examined. OGF-like immunoreactivity was detected in the retina at gestation day (E) 20, but not at E18, and was localized to ganglion cell and neuroblast layers; immunochemical reaction was no longer seen in the retina by postnatal day 6. Native OGF was further identified and characterized by high-performance liquid chromatography (HPLC) studies and immunodot assays, which revealed that [Met5]-enkephalin was present in the neonatal, but not adult, rat retina. OGF binding activity was detected as early as E18 using [125I]-[Met5]-enkephalin and in vitro receptor autoradiography. Little OGF binding activity was noted for prenatal retinas, but appreciable activity was observed from birth to postnatal day 4; no OGF binding could be detected after postnatal day 5 or in the adult. These results reveal the transient appearance of the OGF, [Met5]-enkephalin, and its receptor binding activity in the developing mammalian retina, and show that their ontogeny coincides with the timetable of DNA synthesis of retinal neuroblasts.

Opioid growth factor inhibits DNA synthesis in mouse tongue epithelium in a circadian rhythm-dependent manner

1994 ◽  
Vol 267 (3) ◽  
pp. R645-R652 ◽  
Author(s):  
I. S. Zagon ◽  
Y. Wu ◽  
P. J. McLaughlin
Keyword(s):  
Circadian Rhythm ◽  
Growth Factor ◽  
Dna Synthesis ◽  
Opioid Peptide ◽  
Endogenous Opioids ◽  
Opioid Antagonist ◽  
Dependent Manner ◽  
Endogenous Opioid ◽  
Endogenous Opioid Peptide ◽  
Opioid Growth Factor

In addition to neuromodulation, endogenous opioids also serve as growth factors. To investigate the involvement of the naturally occurring opioid peptide [Met5]enkephalin [termed opioid growth factor (OGF)] in the renewal of epithelium, adult mice were given systemic injections of OGF (1 mg/kg) and examined 2 h later at 0700 or 1700 h. DNA synthesis in the tongue was investigated using [3H]thymidine and autoradiography. OGF depressed DNA synthesis of the basal epithelial cells in the tip, and dorsal and ventral surfaces of the tongue (42-44% of control levels) only at 0700 h. This decrease in DNA synthesis was blocked by concomitant administration of the opioid antagonist naloxone (10 mg/kg); naloxone alone had no influence on cell replicative processes. Both OGF and its receptor, zeta (zeta), were detected in the stratified squamous epithelium of the ventral and dorsal surfaces of the tongue by immunocytochemistry. Photodensitometric measurements of immunocytochemical preparations revealed almost twofold more OGF and zeta-receptor immunoreactivity at 1700 h than at 0700 h. These results indicate that an endogenous opioid peptide and its receptor are present and govern cellular renewal processes in the tongue and regulate DNA synthesis in a circadian rhythm-dependent fashion.

Opioid growth factor is present in human and mouse gastrointestinal tract and inhibits DNA synthesis

1997 ◽  
Vol 272 (4) ◽  
pp. R1094-R1104
Author(s):  
I. S. Zagon ◽  
Y. Wu ◽  
P. J. McLaughlin
Keyword(s):  
Circadian Rhythm ◽  
Growth Factor ◽  
Epithelial Cells ◽  
Dna Synthesis ◽  
Opioid Antagonist ◽  
Receptor Interaction ◽  
Esophageal Epithelium ◽  
Endogenous Opioid ◽  
Endogenous Opioid Peptide ◽  
Opioid Growth Factor

Native opioid peptides serve as growth factors in a number of normal and neoplastic cells and tissues. This study investigated the influence of opioids on circadian rhythm-dependent DNA synthesis in mouse esophagus during homeostatic renewal. In contrast to a labeling index (LI) of 24.0% at 0630 and 5.5% at 1600, disruption of opioid-receptor interaction by the potent opioid antagonist naltrexone hydrochloride (NTX; 10 mg/kg) in mice resulted in an elevation of 49% in DNA synthesis of esophageal epithelial cells at 1600, but had no effect at 0630. Mice subjected to [Met5]enkephalin (1 mg/kg) had an LI that was decreased 23% from control levels at 0630, but was unaffected at 1600. This decrease in DNA synthesis was blocked by concomitant administration of naloxone (10 mg/kg); naloxone alone had no influence on cell replicative processes. In tissue culture studies, NTX and OGF markedly increased and decreased, respectively, the LI from control values. Both opioid growth factor (OGF) and its receptor, zeta, were detected in all but the cornified layer of mouse esophageal epithelium and in the epithelial cells of the stomach and small and large intestines. In addition, both peptide and receptor were observed in the basal and suprabasal cells of human esophageal epithelium. These results indicate that an endogenous opioid peptide (OGF) and its receptor (zeta) reside in gastrointestinal epithelium and play a role in cellular renewal processes in a tonically inhibitory, direct, and circadian rhythm-dependent fashion.

Opioid growth factor-dependent DNA synthesis in the neonatal rat aorta

1996 ◽  
Vol 270 (1) ◽  
pp. R22-R32
Author(s):  
I. S. Zagon ◽  
Y. Wu ◽  
P. J. McLaughlin
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Dna Synthesis ◽  
Cell Types ◽  
Opioid Peptide ◽  
Endogenous Opioids ◽  
Negative Regulator ◽  
Neonatal Rat ◽  
Endogenous Opioid Peptide ◽  
Opioid Growth Factor

In addition to neuromodulation, endogenous opioids serve as growth factors in neural and nonneural cells. This study examined the hypothesis that opioids are inhibitory growth factors in vascular development. No circadian rhythm was detected for DNA synthesis in endothelial, smooth muscle, or fibroblast cells in the aorta of 1-day-old rats. Administration of naltrexone (NTX), a potent opioid antagonist, markedly increased the labeling indexes of all three cell types. [Met5]enkephalin, found to be the only opioid peptide to influence DNA synthesis and termed the opioid growth factor (OGF), depressed DNA synthesis in each cell type for 4-6 h in a dose-dependent and receptor-mediated manner. In aortas placed in tissue culture, DNA synthesis was significantly increased by incubation in NTX and decreased by incubation with OGF, Both OGF and its receptor, zeta (zeta), were associated with the cytoplasm of all three cell types in the neonatal aorta. These results indicate that an endogenous opioid peptide (i.e., OGF) and its receptor (i.e., zeta) reside in the developing vascular cells and govern DNA synthesis, with OGF acting directly as a tonic negative regulator of cell generation in the great vessels.

Endogenous opioid peptide modulation of LH secretion in the ewe lamb: possible involvement of 5-hydroxytryptamine

1988 ◽  
Vol 116 (3) ◽  
pp. 403-411 ◽  
Author(s):  
S. C. Stansfield ◽  
P. G. Knight ◽  
C. M. Howles ◽  
F. J. Cunningham
Keyword(s):  
Limit Of Detection ◽  
Plasma Concentrations ◽  
Opioid Peptide ◽  
Prolactin Secretion ◽  
Endogenous Opioid ◽  
Concurrent Administration ◽  
Endogenous Opioid Peptide ◽  
Ewe Lambs

ABSTRACT Evidence from several species suggests that the endogenous opioid peptides participate in the regulation of gonadotrophin and prolactin secretion. The aim of the present study involving intact and ovariectomized prepubertal ewe lambs was to compare the effects in vivo of an opioid peptide agonist d-Ala2,N-Phe4,Met(0)ol5]-enkephalin (FK 33–824) and antagonist, naloxone, on concentrations of LH and prolactin in plasma, and levels of neurotransmitter metabolites in cerebrospinal fluid (CSF), with their effects in vitro on the release of gonadotrophin-releasing hormone (GnRH) and neurotransmitters from isolated median eminences. Infusion of FK 33–824 (0·5 mg/30 min) in vivo depressed plasma LH levels in both intact and ovariectomized lambs; this effect could be reversed by naloxone. In ovariectomized lambs, the inhibitory action of FK 33–824 on plasma LH levels was associated with a 13% rise in the concentration of the metabolite of 5-hydroxytryptamine, 5-hydroxyindolacetic acid (5-HIAA). Concurrent administration of naloxone resulted in an abrupt 33% fall in CSF levels of 5-HIAA. No significant changes in plasma concentrations of prolactin or CSF concentrations of the metabolites of dopamine were observed in response to the administration of FK 33–824 or FK 33–824 plus naloxone. That FK 33–824 inhibited LH release through a central mechanism was confirmed using superfused median eminences in vitro. Thus FK 33–824 (1 μmol/l) greatly diminished the release of GnRH induced by the introduction of a depolarizing stimulus (36 mmol K+/l) in tissue obtained from both intact and ovariectomized ewe lambs. Since neurotransmitter levels in superfusate samples were below the limit of detection of the high-performance liquid chromatography assay, it remains to be ascertained whether FK 33–824 concomitantly affected neurotransmitter release. These results lead us to conclude that FK 33–824 inhibits the secretion of LH, but not prolactin, in intact and ovariectomized prepubertal ewe lambs. The action of FK 33–824 is mediated, at the level of the median eminence, through a reduction of GnRH release. It is tentatively suggested that FK 33–824 may exert this inhibitory effect by stimulating the release of 5-hydroxytryptamine. J. Endocr. (1988) 116, 403–411

scholarly journals Effects of the endogenous opioid peptide, endomorphin 1, on supraoptic nucleus oxytocin and vasopressin neurones in vivo and in vitro

2001 ◽  
Vol 132 (5) ◽  
pp. 1136-1144 ◽  
Author(s):  
Naomi Doi ◽  
Colin H Brown ◽  
Helena Delgado Cohen ◽  
Gareth Leng ◽  
John A Russell
Keyword(s):  
Supraoptic Nucleus ◽  
Opioid Peptide ◽  
Endogenous Opioid ◽  
Endogenous Opioid Peptide

QS297. Opioid Growth Factor Inhibits Cell Replication and DNA Synthesis of Hepatocellular Cancer In Vitro Through a Receptor Mediated Mechanism

2009 ◽  
Vol 151 (2) ◽  
pp. 296
Author(s):  
D.M. Avella Patino ◽  
H.R. Tagaram ◽  
E.T. Kimchi ◽  
P.J. McLaughlin ◽  
I.S. Zagon ◽  
...  
Keyword(s):  
Growth Factor ◽  
Dna Synthesis ◽  
Hepatocellular Cancer ◽  
Cell Replication ◽  
Opioid Growth Factor

Involvement of endogenous opioid peptides in the neuroendocrine response of ewe lambs to the introduction of a ram

1987 ◽  
Vol 115 (2) ◽  
pp. 333-339 ◽  
Author(s):  
S. C. Stansfield ◽  
P. G. Knight ◽  
N. Z. Al-Mauly ◽  
M. J. Bryant
Keyword(s):  
Median Eminence ◽  
Reproductive Activity ◽  
Pulse Frequency ◽  
Opioid Peptide ◽  
Endogenous Opioid ◽  
Endogenous Opioid Peptide ◽  
Ewe Lambs ◽  
Basal Release

ABSTRACT Prepubertal ewes can, under certain circumstances, be stimulated to ovulate by the novel introduction of a ram. The endocrine response to the presence of the ram is characterized by a rapid increase in the frequency of episodic release of LH. The purpose of this study was to investigate the effect of the presence of a ram on LH pulse frequency in vivo, gonadotrophin-releasing hormone (GnRH) and β-endorphin concentrations in the median eminence, and on the influence of the endogenous opioid peptide agonist [d-Ala2,N-Phe4,Met(0)ol5]-enkephalin (FK 33–824) on basal and depolarization-induced release of GnRH from median eminence tissue superfused in vitro. The study was performed at two prepubertal ages in August and September. In September, the introduction of a ram resulted in an increase in pulsatile release of LH, which was associated with an increase in the rate of basal release of GnRH from median eminence tissue superfused in vitro, and the development of a marked ability of FK 33–824 to suppress depolarization-induced release of GnRH. The concentration of β-endorphin in the median eminence was reduced in animals exposed to the ram at this time. In contrast, the introduction of a ram in August failed to stimulate an increase in LH pulse frequency, basal release of GnRH in vitro was not altered and FK 33–824 was ineffective in reducing depolarization-induced release of GnRH. These results suggest that the premature onset of reproductive activity induced by exposure to the ram may involve the participation of the endogenous opioid peptide system. J. Endocr. (1987) 115, 333–339

Adrenergic mediation of the naloxone-induced GnRH release from hypothalami of ovariectomized, steroid-treated immature rats

1991 ◽  
Vol 125 (6) ◽  
pp. 680-686 ◽  
Author(s):  
K. Kim ◽  
B. J. Lee ◽  
C. C. Lee ◽  
W. K. Cho ◽  
V. D. Ramirez
Keyword(s):  
Adrenergic Receptor ◽  
Opioid Peptide ◽  
Spontaneous Release ◽  
Endogenous Opioid ◽  
Endogenous Opioid Peptide ◽  
Immature Rats ◽  
Gnrh Release ◽  
Diethyldithiocarbamic Acid ◽  
Adrenergic Neurotransmission

Abstract. The present study examines the effect of naloxone on GnRH release in vitro under different steroid milieus. Naloxone (6.1 μmol/kg) administered 30 min before decapitation was highly effective in evoking GnRH release from superfused hypothalamic tissues derived from ovariectomized, estradiol- and progesteronetreated immature rats, while ineffective in altering GnRH release from intact, ovariectomized and vehicle- or estradiol-treated rats. To further explore the possible involvement of catecholamines in the naloxone-stimulated GnRH release, diethyldithiocarbamic acid (2.9 mmol/kg), an inhibitor of noradrenalin synthesis, was administered ip 30 min before naloxone injection into ovariectomized, estradiol- and progesterone-treated rats. Diethyldithiocarbamic acid markedly reduced the naloxone-evoked GnRH release, although it was ineffective in modifying the spontaneous release of GnRH. A blockade of α-adrenergic receptor with phenoxybenzamine significantly suppressed the naloxone-stimulated GnRH release, whereas treatment with propranolol, a β-adrenergic receptor blocker, failed to alter GnRH release. The present data suggest that the endogenous opioid peptide may participate in the regulation of GnRH release under a particular steroid milieu, and the inhibitory action of endogenous opioid peptide seems to require the mediation of adrenergic neurotransmission, presumably through α-adrenergic receptor.

Opioid growth factor modulates corneal epithelial outgrowth in tissue culture

1995 ◽  
Vol 268 (4) ◽  
pp. R942-R950 ◽  
Author(s):  
I. S. Zagon ◽  
J. W. Sassani ◽  
P. J. McLaughlin
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Opioid Receptor ◽  
Corneal Epithelium ◽  
Labeling Index ◽  
Opioid Antagonist ◽  
Receptor Interaction ◽  
Endogenous Opioid ◽  
Endogenous Opioid Peptide ◽  
Opioid Growth Factor

In addition to neuromodulation, endogenous opioid peptides serve as growth factors. To determine involvement of opioids in the homeostatic renewal and repair of the corneal epithelium, epithelial outgrowths from 3-mm explants of rabbit cornea were investigated. Blockade of opioid-receptor interaction by the potent opioid antagonist naltrexone (NTX) for 7 days significantly increased the extent of outgrowths and the number and labeling index (DNA synthesis) of epithelial cells, relative to control levels. Outgrowths exposed to the opioid growth factor (OGF) [Met5]enkephalin for 7 days were subnormal in extent and labeling index and displayed alterations in architectural pattern. The effects of OGF on epithelial outgrowth were blocked by concomitant exposure to the opioid antagonist naloxone; naloxone alone had no effect on growth at the concentration utilized. NTX and OGF were active in both serum-containing and serum-free cultures. Immunocytochemical investigations showed that both OGF and its opioid receptor zeta (zeta) were present in epithelial cells growing in control media. The results indicate that an endogenous opioid peptide and its receptor are present in mammalian corneal epithelium and serve to modulate cell proliferation, migration, and organization.

scholarly journals Imaging Endogenous Opioid Peptide Release with [11C]Carfentanil and [3H]Diprenorphine: Influence of Agonist-Induced Internalization

2014 ◽  
Vol 34 (10) ◽  
pp. 1604-1612 ◽  
Author(s):  
Darren R Quelch ◽  
Loukia Katsouri ◽  
David J Nutt ◽  
Christine A Parker ◽  
Robin J Tyacke
Keyword(s):  
Confocal Microscopy ◽  
Neurotransmitter Release ◽  
Radioligand Binding ◽  
Subcellular Fractionation ◽  
Opioid Peptide ◽  
Binding Studies ◽  
Endogenous Opioid ◽  
Double Labeling ◽  
Endogenous Opioid Peptide

Understanding the cellular processes underpinning the changes in binding observed during positron emission tomography neurotransmitter release studies may aid translation of these methodologies to other neurotransmitter systems. We compared the sensitivities of opioid receptor radioligands, carfentanil, and diprenorphine, to amphetamine-induced endogenous opioid peptide (EOP) release and methadone administration in the rat. We also investigated whether agonist-induced internalization was involved in reductions in observed binding using subcellular fractionation and confocal microscopy. After radioligand administration, significant reductions in [11C]carfentanil, but not [3H]diprenorphine, uptake were observed after methadone and amphetamine pretreatment. Subcellular fractionation and in vitro radioligand binding studies showed that amphetamine pretreatment only decreased total [11C]carfentanil binding. In vitro saturation binding studies conducted in buffers representative of the internalization pathway suggested that μ-receptors are significantly less able to bind the radioligands in endosomal compared with extracellular compartments. Finally, a significant increase in μ-receptor-early endosome co-localization in the hypothalamus was observed after amphetamine and methadone treatment using double-labeling confocal microscopy, with no changes in δ- or κ-receptor co-localization. These data indicate carfentanil may be superior to diprenorphine when imaging EOP release in vivo, and that alterations in the ability to bind internalized receptors may be a predictor of ligand sensitivity to endogenous neurotransmitter release.

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