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 (β-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 Leuenkephalin, 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 μ, δ and κ receptors respectively) showed that the effect of opioid peptides on the zona glomerulosa appeared to be mediated exclusively by μ receptors while the response of inner zone cells was mediated by both μ and, to a lesser extent, κ 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 μ and κ opioid receptors are linked to the activation of phospholipase C.
Journal of Endocrinology (1995) 144, 503–510
Design, synthesis and characterization of a series of 6-substituted-4-hydroxy-1-(2-substituted thiazol-4-yl)quinolin-2(1<em>H</em>)-one derivatives and evaluation of their <em>in vitro </em>anticancer and antibacterial activity
