The prenatal developmental profile of expression of opioid peptides and receptors in the mouse brain

Rius, R.A.; Barg, Jacob; Wojciech, T.; Coscia, Carmine J.; Loh, Y. Peng

doi:10.1016/0165-3806(91)90010-g

Cited by 78 publications

(40 citation statements)

References 46 publications

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“…Taken together, the above results show early receptor gene expression that significantly extends inferences from previous ligand-binding studies showing initial receptor binding activities for and ligands at E12.5 and E14.5, respectively (Rius et al, 1991). The detection of the ␦ receptor mRNA in the DRG at E12.5, the pons at E13.5, and the caudate putamen at E17.5 also significantly extends binding data, which have been unable to detect ␦ binding activity until P1 (Kornblum et al, 1987;Rius et al, 1991).…”

Section: Discussionsupporting

confidence: 72%

“…For example, tissue homogenates generally have been used because of small tissue size, and the CNS usually has been the only tissue examined. In the mouse, receptor binding activity can be detected in homogenates as early as embryonic day 12.5 (E12.5) (Rius et al, 1991), whereas receptor binding is first detected at E14.5. In contrast, CNS ␦ receptor binding sites cannot be detected at all prenatally (Kornblum et al, 1987;Rius et al, 1991).…”

mentioning

confidence: 99%

“…In the mouse, receptor binding activity can be detected in homogenates as early as embryonic day 12.5 (E12.5) (Rius et al, 1991), whereas receptor binding is first detected at E14.5. In contrast, CNS ␦ receptor binding sites cannot be detected at all prenatally (Kornblum et al, 1987;Rius et al, 1991). In the rat spinal cord, and binding sites first appear at E15, whereas ␦ sites are not detected until postnatal day 1 (P1) (Attali et al, 1990).…”

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confidence: 99%

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Developmental Expression of the μ, κ, and δ Opioid Receptor mRNAs in Mouse

Zhu¹,

Hsu²,

Pintar³

1998

J. Neurosci.

153

109

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To characterize further the establishment of the opioid system during prenatal mouse development, we have examined the spatial and temporal expression patterns of , , and ␦ opioid receptor mRNAs and find that the expression patterns of these mRNAs are distinct at all ages. Within the embryo, is the first opioid receptor expressed, with transcripts detected in the gut epithelium as early as embryonic day 9.5 (E9.5). By E10.5, receptor expression is first detected in the facial-vestibulocochlear preganglion complex, whereas ␦ receptor mRNA is first detected at E12.5 in several peripheral tissues, including the olfactory epithelium, heart, limb bud, and tooth. In the brain, both and mRNAs are first detected at E11.5 in the basal ganglia and midbrain, respectively. During mid-gestation and late gestation, the expression of both and receptors extends to other brain regions that exhibit high expression in the adult, including the medial habenula, hypothalamus, pons, and medulla for and the basal ganglia, thalamus, hypothalamus, raphe, and ventral tegmental area for . Thus by E17.5, many aspects of the adult expression patterns of and receptors already have been established. Compared with and , ␦ receptor mRNA expression in the brain begins relatively late, and the expression levels remain very low even at E19.5. In contrast to its late appearance in the brain, however, ␦ is the first opioid receptor expressed in the dorsal root ganglion, at E12.5, before its expression in the spinal cord begins at E15.5. receptor is the first opioid receptor expressed in the spinal cord, at E11.5. These results extend previous ligand-binding data to significantly earlier ages and suggest that early developmental events in both neural and non-neural tissues may be modulated by opioid receptors. Several examples of possible autocrine and paracrine loops of opioid peptide and receptor expression have been identified, suggesting a role for these local circuits in developmental processes.

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Section: Discussionsupporting

confidence: 72%

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confidence: 99%

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confidence: 99%

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Developmental Expression of the μ, κ, and δ Opioid Receptor mRNAs in Mouse

Zhu¹,

Hsu²,

Pintar³

1998

J. Neurosci.

153

109

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“…During mouse embryonic development, the MOR message was specifically observed as early as embryonic day 8.5 (E8.5) using the reverse transcription (RT)-PCR method (44). In contrast, MOR transcripts were detected only beginning at E12 using the radioligand binding method (70) and at E10.5 by in situ hybridization (85). Transcript levels gradually increased throughout embryonic and postnatal stages, reaching a plateau at adulthood (44).…”

mentioning

confidence: 99%

Evidence of Endogenous Mu Opioid Receptor Regulation by Epigenetic Control of the Promoters

Hwang

Song

Kim

et al. 2007

Molecular and Cellular Biology

145

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The pharmacological effect of morphine as a painkiller is mediated mainly via the mu opioid receptor (MOR) and is dependent on the number of MORs in the cell surface membrane. While several studies have reported that the MOR gene is regulated by various cis-and trans-acting factors, many questions remain unanswered regarding in vivo regulation. The present study shows that epigenetic silencing and activation of the MOR gene are achieved through coordinated regulation at both the histone and DNA levels. In P19 mouse embryonal carcinoma cells, expression of the MOR was greatly increased after neuronal differentiation. MOR expression could also be induced by a demethylating agent (5-aza-2-deoxycytidine) or histone deacetylase inhibitors in the P19 cells, suggesting involvement of DNA methylation and histone deacetylation for MOR gene silencing. Analysis of CpG DNA methylation revealed that the proximal promoter region was unmethylated in differentiated cells compared to its hypermethylation in undifferentiated cells. In contrast, the methylation of other regions was not changed in either cell type. Similar methylation patterns were observed in the mouse brain. In vitro methylation of the MOR promoters suppressed promoter activity in the reporter assay. Upon differentiation, the in vivo interaction of MeCP2 was reduced in the MOR promoter region, coincident with histone modifications that are relevant to active transcription. When MeCP2 was disrupted using MeCP2 small interfering RNA, the endogenous MOR gene was increased. These data suggest that DNA methylation is closely linked to the MeCP2-mediated chromatin structure of the MOR gene. Here, we propose that an epigenetic mechanism consisting of DNA methylation and chromatin modification underlies the cell stage-specific mechanism of MOR gene expression.Opioids exert their pharmacological and physiological effects through binding to their endogenous receptors. Three types of opioid receptors, mu (), delta (␦), and kappa (), all belonging to the G-protein-coupled receptor superfamily, have been cloned. Upon agonist binding, these receptors couple to G proteins and affect several signal transduction pathways thought to mediate a broad range of functions and pharmacological effects of endogenous and exogenous opioids (51). Previous studies suggested that the opioid receptor (MOR) plays a key role in mediating the major clinical effects of analgesics, such as morphine, as well as the development of tolerance and physical dependence upon prolonged administration (39). MOR is mainly expressed in the central nervous system, with densities varying greatly in different regions, which can display different functional roles (55). During mouse embryonic development, the MOR message was specifically observed as early as embryonic day 8.5 (E8.5) using the reverse transcription (RT)-PCR method (44). In contrast, MOR transcripts were detected only beginning at E12 using the radioligand binding method (70) and at E10.5 by in situ hybridization (85). Transcript levels gradually incr...

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“…The distribution of m-opioid receptor mRNA in the rat brain increases between embryonic days 16 and 22 and continues to increase until postnatal day 7 to a level equivalent to the adult one (9). The coexistence of mand k-but not d-opioid sites has been reported in the human fetal brain (10), and during early neonatal life in the brain of both rat (11) and mouse (12). The development of opiate receptors in the rat brain may be sex hormone dependent, as 6-day-old females display more opiate-binding sites than age-matched males (13).…”

Section: Introductionmentioning

confidence: 99%

Morphine-induced stimulation of pituitary-adrenocortical activity is mediated by activation of nitric oxide in the early stages of postnatal life in the rat

Lésage

Bernet²,

Montel³

et al. 2001

European Journal of Endocrinology

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Objective: The first aim of the present study was to determine if morphine, a prototypic m-opioid agonist drug, affects pituitary±adrenocortical activity in developing rat pups (first and second weeks of postnatal life). The second aim of this study was to explore, in vivo, if nitric oxide (NO) could be involved in the neurohormonal response to morphine in the early stages of postnatal life. Methods: Plasma ACTH and corticosterone concentrations were determined by RIA in rat pups n 5±14 rats/experimental group) after they had been killed by decapitation. In a first experiment, 1-day and 1-and 2-week-old rats were treated s.c. with morphine (20 mg/kg) or with vehicle (0.9% NaCl) and killed 5±90 min later. In a second experiment, 2-week-old pups were pretreated s.c. with naltrexone (NAL; 0.4 mg/kg or 10 mg/kg), and injected 1 h later with either morphine (20 mg/kg) or vehicle, and killed 30 min later. Some pups injected with only NAL were killed 60 or 90 min later. On the other hand, pups injected with NAL (10 mg/kg) or NAL and morphine were killed 30 min later. In a third experiment, 2-week-old pups were pretreated s.c. with N-v-nitro L arginine methylester (L-NAME; 30 mg/kg or 100 mg/kg), and injected 1 h later with either morphine (20 mg/kg) or vehicle, and killed 30 min later. Moreover, some pups injected with L-NAME (100 mg/kg) or L-NAME with morphine were killed 30 min later. In a final experiment, pups were injected s.c. with either S-nitroso-N-acetylpenicillamine (SNAP; 5 mg/kg) or vehicle, and killed 60 or 90 min later. Results: Morphine administered to rat pups elicited marked rises in both ACTH and corticosterone secretion. Moreover, these responses increased with advancing postnatal age. In 2-week-old rat pups, NAL, a competitive antagonist at m-opioid receptors, administered alone increased both plasma ACTH and corticosterone concentrations 30 min later. L-NAME, a specific NO synthase inhibitor, did not affect plasma ACTH and corticosterone concentrations 30 min later when administered alone. NAL, when concomitantly administered with morphine, was unable to block morphine responses. In contrast, morphine responses were blocked by pretreatment (60 min before) with NAL or with L-NAME. Acute injection of SNAP increased both ACTH and corticosterone release. Conclusion: Our results suggest that opioids have controversial effects on pituitary±adrenocortical activity in the early postnatal period in the rat, and that endogenous NO is one of the major factors in the response of the pituitary±adrenocortical axis to morphine.

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The prenatal developmental profile of expression of opioid peptides and receptors in the mouse brain

Cited by 78 publications

References 46 publications

Developmental Expression of the μ, κ, and δ Opioid Receptor mRNAs in Mouse

Developmental Expression of the μ, κ, and δ Opioid Receptor mRNAs in Mouse

Evidence of Endogenous Mu Opioid Receptor Regulation by Epigenetic Control of the Promoters

Morphine-induced stimulation of pituitary-adrenocortical activity is mediated by activation of nitric oxide in the early stages of postnatal life in the rat

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