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

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 Orphanin FQ: Evidence for a Role in the Control of the Reproductive Neuroendocrine System

Endocrinology ◽  
2007 ◽  
Vol 148 (10) ◽  
pp. 4993-5001 ◽  
Author(s):  
Chad D. Foradori ◽  
Marcel Amstalden ◽  
Lique M. Coolen ◽  
Sushma R. Singh ◽  
Christine J. McManus ◽  
...  
Keyword(s):  
Pulse Amplitude ◽  
Pulse Frequency ◽  
Brain Regions ◽  
Orphanin Fq ◽  
Endogenous Opioid ◽  
Endogenous Opioid Peptide ◽  
External Zone ◽  
Gnrh Secretion

Orphanin FQ (OFQ), also known as nociceptin, is a member of the endogenous opioid peptide family that has been functionally implicated in the control of pain, anxiety, circadian rhythms, and neuroendocrine function. In the reproductive system, endogenous opioid peptides are involved in the steroid feedback control of GnRH pulses and the induction of the GnRH surge. The distribution of OFQ in the preoptic area and hypothalamus overlaps with GnRH, and in vitro evidence suggests that OFQ can inhibit GnRH secretion from hypothalamic fragments. Using the sheep as a model, we examined the potential anatomical colocalization between OFQ and GnRH using dual-label immunocytochemistry. Confocal microscopy revealed that approximately 93% of GnRH neurons, evenly distributed across brain regions, were also immunoreactive for OFQ. In addition, almost all GnRH fibers and terminals in the external zone of the median eminence, the site of neurosecretory release of GnRH, also colocalized OFQ. This high degree of colocalization suggested that OFQ might be functionally important in controlling reproductive endocrine events. We tested this possibility by examining the effects of intracerebroventricular administration of [Arg14, Lys15] OFQ, an agonist to the OFQ receptor, on pulsatile LH secretion. The agonist inhibited LH pulse frequency in both luteal phase and ovariectomized ewes and suppressed pulse amplitude in the latter. The results provide in vivo evidence supporting a role for OFQ in the control of GnRH secretion and raise the possibility that it acts as part of an ultrashort, autocrine feedback loop controlling GnRH pulses.

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

Seasonal and steroid-dependent effects on the modulation of LH secretion in the ewe by intracerebroventricularly administered β-endorphin or naloxone

1989 ◽  
Vol 122 (2) ◽  
pp. 509-517 ◽  
Author(s):  
R. J. E. Horton ◽  
H. Francis ◽  
I. J. Clarke
Keyword(s):  
Breeding Season ◽  
Luteal Phase ◽  
Pulse Frequency ◽  
Opioid Peptide ◽  
Follicular Phase ◽  
Oestrous Cycle ◽  
Opioid Antagonist ◽  
Endogenous Opioid ◽  
Endogenous Opioid Peptide ◽  
Lh Secretion

ABSTRACT The natural opioid ligand, β-endorphin, and the opioid antagonist, naloxone, were administered intracerebroventricularly (i.c.v.) to evaluate effects on LH secretion in ovariectomized ewes and in ovariectomized ewes treated with oestradiol-17β plus progesterone either during the breeding season or the anoestrous season. Ovary-intact ewes were also studied during the follicular phase of the oestrous cycle. Jugular blood samples were taken at 10-min intervals for 8 h and either saline (20–50 μl), 100 μg naloxone or 10 μg β-endorphin were injected i.c.v. after 4 h. In addition, luteal phase ewes were injected i.c.v. with 25 μg β-endorphin(1–27), a purported endogenous opioid antagonist. In ovariectomized ewes, irrespective of season, saline and naloxone did not affect LH secretion, but β-endorphin decreased the plasma LH concentrations, by reducing LH pulse frequency. The effect of β-endorphin was blocked by administering naloxone 30 min beforehand. Treating ovariectomized ewes with oestradiol-17β plus progesterone during the breeding season reduced plasma LH concentrations from 6–8 μg/l to less than 1 μg/l. In these ewes, saline did not alter LH secretion, but naloxone increased LH pulse frequency and the plasma concentrations of LH within 15–20 min. During anoestrus, the combination of oestradiol-17β plus progesterone to ovariectomized ewes reduced the plasma LH concentrations from 3–5 μg/l to undetectable levels, and neither saline nor naloxone affected LH secretion. During the follicular phase of the oestrous cycle, naloxone enhanced LH pulse frequency, which resulted in increased plasma LH concentrations; saline had no effect. In these sheep, β-endorphin decreased LH pulse frequency and the mean concentrations of LH, and this effect was prevented by the previous administration of naloxone. The i.c.v. administration of β-endorphin(1–27) to luteal phase ewes did not affect LH secretion. These data demonstrate the ability of a naturally occurring opioid peptide to inhibit LH secretion in ewes during the breeding and non-breeding seasons, irrespective of the gonadal steroid background. In contrast, whilst the gonadal steroids suppress LH secretion in ovariectomized ewes during both seasons, they only appear to activate endogenous opioid peptide (EOP)-mediated inhibition of LH secretion during the breeding season. Furthermore, these data support the notion that LH secretion in ovariectomized ewes is not normally under the control of EOP, so that naloxone has no effect. Journal of Endocrinology (1989) 122, 509–517

Opioid peptides and testicular activity in the lizard Podarcis s. sicula Raf

1994 ◽  
Vol 143 (3) ◽  
pp. 565-571 ◽  
Author(s):  
G Ciarcia ◽  
F Facchinetti ◽  
M Vallarino ◽  
M Pestarino ◽  
M Paolucci ◽  
...  
Keyword(s):  
Opioid Peptides ◽  
High Performance ◽  
Physiological Role ◽  
Reproductive Activity ◽  
Opioid System ◽  
Endogenous Opioid System ◽  
Endogenous Opioid ◽  
Naltrexone Treatment

Abstract In mammals endorphinergic systems have been shown to modulate reproductive processes and β-endorphin (β-EP) has been found to influence sexual functions, acting at the hypothalamus-pituitary-gonadal axis level. Using immunocytochemical and in vitro studies, evidence for a diffuse pro-opiomelanocortin-related opioid system in the lizard Podarcis s. sicula was produced. In the testis, β-EP immunoreactivity showed seasonal variation, being most pronounced in the interstitial cells of sexually quiescent lizards (December). Reverse-phase high-performance liquid chromatography, coupled with radioimmunoassay and immunocytochemistry, showed that β-EP and acetyl β-EP increased during December, while their concentrations were low during April, when the highest testicular activity occurred. Using in vivo studies, it was found that naltrexone treatment, blocking pituitary opioid receptor, increased androgen levels in the plasma and in the testis. It was also found with in vitro studies that the endogenous opioid system inhibits gonadotrophin release and therefore androgen production by the testis. The data reported here provide evidence for the physiological role played by opioid peptides at the pituitary level to regulate the seasonal reproductive activity of the lizard Podarcis s. sicula. Journal of Endocrinology (1994) 143, 565–571

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.

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.

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.

scholarly journals An Effective and Safe Enkephalin Analog for Antinociception

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 927
Author(s):  
KK DurgaRao Viswanadham ◽  
Roland Böttger ◽  
Lukas Hohenwarter ◽  
Anne Nguyen ◽  
Elham Rouhollahi ◽  
...  
Keyword(s):  
Physical Dependence ◽  
Opioid Peptide ◽  
Vehicle Group ◽  
Endogenous Opioid ◽  
Endogenous Opioid Peptide ◽  
Extended Plasma ◽  
The Central Nervous System ◽  
Overdose Deaths ◽  
Plasma Half Life ◽  
Small Hydrophobic

Opioids account for 69,000 overdose deaths per annum worldwide and cause serious side effects. Safer analgesics are urgently needed. The endogenous opioid peptide Leu-Enkephalin (Leu-ENK) is ineffective when introduced peripherally due to poor stability and limited membrane permeability. We developed a focused library of Leu-ENK analogs containing small hydrophobic modifications. N-pivaloyl analog KK-103 showed the highest binding affinity to the delta opioid receptor (68% relative to Leu-ENK) and an extended plasma half-life of 37 h. In the murine hot-plate model, subcutaneous KK-103 showed 10-fold improved anticonception (142%MPE·h) compared to Leu-ENK (14%MPE·h). In the formalin model, KK-103 reduced the licking and biting time to ~50% relative to the vehicle group. KK-103 was shown to act through the opioid receptors in the central nervous system. In contrast to morphine, KK-103 was longer-lasting and did not induce breathing depression, physical dependence, and tolerance, showing potential as a safe and effective analgesic.

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