Ontogeny of μ- and κ-Opiate Receptor Control of the Hypothalamo-Pituitary-Adrenal Axis in Rats*

Adamson, William; Windh, Rolf T.; Blackford, S.; Kuhn, Cynthia M.

doi:10.1210/endo-129-2-959

Cited by 43 publications

(26 citation statements)

References 46 publications

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“…The ACTH response to the nonopioid peptide fragment, Dyn A 2-17 , in combination with the lack of ACTH release in response to the highly selective ĸ-opioid receptor agonist, U50488H, is consistent with the involvement of nonopioid mechanisms. These findings are unlike previous findings in rats, showing that ĸ-opioid receptors may play a role in regulating the HPA axis [10, 11, 12]. This discrepancy suggests the involvement of opioid receptors in the regulation of the hypothalamic-pituitary axis, but not at the level of the pituitary.…”

Section: Discussioncontrasting

confidence: 99%

Dynorphin Stimulates Corticotropin Release from Mouse Anterior Pituitary AtT-20 Cells through Nonopioid Mechanisms

Cheng

Birk²,

Gershengorn³

et al. 2000

Neuroendocrinology

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Dynorphin (Dyn) peptides were previously shown to increase plasma corticotropin (ACTH) in the ovine fetus, but the site of its action remains unclear. In the present study, Dyn A_1-17 was found to stimulate ACTH release from mouse anterior pituitary tumor AtT-20 cells in a dose-dependent manner. Naloxone did not block the effect of Dyn A_1-17 and the selective ĸ-opioid receptor agonist U50488H did not stimulate ACTH release. Dyn A_2-17, a degradative peptide fragment that does not bind to opioid receptors, also stimulated ACTH release from AtT-20 cells. Although the nonopioid effects of Dyn have previously been attributed to N-methyl-D-aspartate (NMDA) receptors, the ACTH-releasing effects of Dyn A_1-17 in AtT-20 cells were not affected by co-administration of NMDA receptor antagonist LY235959. The ACTH response to Dyn A_1-17 could not be blocked by α-helical CRH (CRH antagonist) and was additive with a maximal stimulatory dose of CRH, suggesting different mechanisms of action. These results show that the release of ACTH by Dyn A_1-17 in AtT-20 cells is not mediated by ĸ-opioid receptors or by the NMDA receptor.

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Section: Discussioncontrasting

confidence: 99%

Dynorphin Stimulates Corticotropin Release from Mouse Anterior Pituitary AtT-20 Cells through Nonopioid Mechanisms

Cheng

Birk²,

Gershengorn³

et al. 2000

Neuroendocrinology

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“…In this study, we have shown that an acute administration of morphine was able to induce a drastic and long-lasting pituitary±adrenal stimulation in 2-week-old newborns; by contrast, HPA axis activation was more transient and/or less robust in younger pups. ACTH and corticosterone release induced by morphine has been reported previously in 10-day-old rat pups (23). In agreement with our results, these authors reported that morphine-induced corticosterone release was lower on day 5 than on day 15 of postnatal life (23).…”

Section: Discussionsupporting

confidence: 94%

“…ACTH and corticosterone release induced by morphine has been reported previously in 10-day-old rat pups (23). In agreement with our results, these authors reported that morphine-induced corticosterone release was lower on day 5 than on day 15 of postnatal life (23).…”

Section: Discussionsupporting

confidence: 94%

“…One can speculate that m-opiate receptors may be involved in the control of pituitary±adrenal function in early postnatal development; however, they showed controversial effects. This hypothesis is consistent with the development of m-receptors in the rat brain during the perinatal period (9) as well as of other opiate receptors including k-receptors, which are detected in the brain of neonatal rats (11), and may be implicated in the control of the pituitary±adrenal axis within the first week of postnatal life (23). In adults, according to experiments performed in vivo and in vitro, the facilitation of ACTH secretion by morphine was correlated with the release of CRF (15,26,27).…”

Section: Discussionsupporting

confidence: 85%

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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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“…Opioid peptides and their receptors are known to be involved in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis, a major antistress system of mammals [9, 10, 11]. Especially, the POMC gene expressed in the anterior pituitary encodes both adrenocorticotropin (ACTH), a key regulator of the HPA axis, and β-endorphin, one of the endogenous µ-agonists.…”

Section: Introductionmentioning

confidence: 99%

Effects of Loperamide and Other Opioid-Related Substances on the Transcriptional Regulation of the Rat Pro-Opiomelanocortin Gene in AtT20 Cells

Nomura¹,

Iwasaki

Aoki³

et al. 2001

Neuroendocrinology

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Although opioid peptides are involved in the regulation of the hypothalamic-pituitary-adrenal axis, their role in pro-opiomelanocortin (POMC) gene expression at the pituitary level is not known. We therefore examined the effects of opioid receptor agonists, including recently discovered endogenous opioid peptides, on POMC gene expression using the AtT20PL cell line, a subclone of AtT20 in which the rat POMC 5′-promoter-luciferase fusion gene was stably incorporated. The endogenous µ-opioid receptor agonists endomorphin 1 and 2 had no effect on either basal or corticotropin-stimulating-hormone-induced POMC expression. This was also the case with the δ-agonist BUBUC, the ĸ-agonist U50488H and the orphan receptor agonist orphanin FQ. In contrast, the synthetic µ-agonist loperamide significantly inhibited basal and yet enhanced cAMP-induced POMC expression. The inhibitory effect of loperamide was mimicked by the calmodulin antagonist W7 and antagonized by the calcium channel blocker nifedipine, whereas neither the inhibitory nor the enhancing effect of loperamide was influenced by the opioid antagonist naloxone. These results suggest that the synthetic µ-agonist loperamide has a modulatory effect on the 5′-promoter activity of the POMC gene. This effect does not seem to be mediated through the classical µ-opioid receptor but rather in part through a calcium/calmodulin-related mechanism.

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Ontogeny of μ- and κ-Opiate Receptor Control of the Hypothalamo-Pituitary-Adrenal Axis in Rats*

Cited by 43 publications

References 46 publications

Dynorphin Stimulates Corticotropin Release from Mouse Anterior Pituitary AtT-20 Cells through Nonopioid Mechanisms

Dynorphin Stimulates Corticotropin Release from Mouse Anterior Pituitary AtT-20 Cells through Nonopioid Mechanisms

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

Effects of Loperamide and Other Opioid-Related Substances on the Transcriptional Regulation of the Rat Pro-Opiomelanocortin Gene in AtT20 Cells

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