Action of opioid peptides on the rat adrenal cortex: stimulation of steroid secretion through a specific μ opioid receptor

Abstract

While there have been several studies on the actions of opioid peptides on adrenocortical steroidogenesis, the results of these studies have failed to resolve the question as to whether these peptides exert a direct action on the adrenal cortex. The present studies were designed to address this question directly, using collagenase-dispersed rat zona glomerulosa and zonae fasciculata/reticularis cells incubated in vitro. The results obtained clearly show that the opioid peptides tested (beta-endorphin, Leu-enkephalin, Met-enkephalin, and its long-acting analogue, DALA) all exerted a significant stimulatory effect on aldosterone secretion by zona glomerulosa cells and all, except Leu-enkephalin, stimulated corticosterone secretion by inner zone cells. The response was shown to be inhibited by naloxone. There did not appear to be a significant interaction between the effects of ACTH and the opioid peptides on adrenocortical cells. Studies using specific agonists for opioid receptor subtypes (DAMGO, DPDPE and U-50488H, specific for mu, delta and kappa receptors respectively) showed that the effect of opioid peptides on the zona glomerulosa appeared to be mediated exclusively by mu receptors while the response of inner zone cells was mediated by both mu and, to a lesser extent, kappa receptors. Finally, studies on the second messenger systems activated by the opioid peptides and the receptor agonists showed that these peptides act to increase labelling of inositol trisphosphate, and strongly suggest that, in the rat adrenal cortex, both mu and kappa opioid receptors are linked to the activation of phospholipase C.

The Mu-Opioid Receptor Polymorphism A118G Predicts Cortisol Responses to Naloxone and Stress

“…Such an action could affect cortisol production or release independent of ACTH. Indeed, one study demonstrated that opioid peptides stimulate corticosterone secretion by inner zone cells of the rat adrenal cortex in vitro, and that this effect is blocked by naloxone (Kapas et al, 1995). We should also be clear that our findings, regardless of where it is affecting HPA axis function, may not be the result of the A118G SNP itself.…”

Levels and circadian rhythmicity of plasma ACTH, cortisol, and β-endorphin as a function of family history of alcoholism

“…Indeed, it was shown that opioid peptides stimulated the release of corticosterone by cells of the adrenal cortex in vitro. This effect was blocked by the opioid antagonist naloxone (Kapas et al 1995).…”

Adrenal insufficiency in patients on long‐term opioid analgesia

“…In rat adrenal cell culture experiments, administration of opioid peptides resulted in corticosterone production, which was diminished by naloxone. 16 In vivo, morphine potentiated and naloxone inhibited corticosterone production in hypophysectomized rats. 17 If similar mechanisms exist in humans, a pattern of low morning cortisol, blunted ACTH-stimulated cortisol and loss of diurnal rhythm could occur during chronic opioid exposure.…”

“…Opioids may have direct effects upon adrenal glucocorticoid production, based on previous studies in rodents. In rat adrenal cell culture experiments, administration of opioid peptides resulted in corticosterone production, which was diminished by naloxone . In vivo , morphine potentiated and naloxone inhibited corticosterone production in hypophysectomized rats .…”