Kapas S, Purbrick A, Hinson J P
Department of Biochemistry, Faculty of Basic Medical Sciences, Queen Mary and Westfield College, London, UK.
J Endocrinol. 1995 Mar;144(3):503-10. doi: 10.1677/joe.0.1440503.
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.
虽然已有多项关于阿片肽对肾上腺皮质类固醇生成作用的研究，但这些研究结果未能解决这些肽是否对肾上腺皮质有直接作用这一问题。本研究旨在直接解决这个问题，使用体外培养的经胶原酶分散的大鼠肾小球带和束状带/网状带细胞。所获得的结果清楚地表明，所测试的阿片肽（β-内啡肽、亮氨酸脑啡肽、甲硫氨酸脑啡肽及其长效类似物DALA）均对肾小球带细胞的醛固酮分泌产生显著的刺激作用，并且除亮氨酸脑啡肽外，均刺激内层带细胞的皮质酮分泌。该反应被纳洛酮抑制。促肾上腺皮质激素（ACTH）和阿片肽对肾上腺皮质细胞的作用之间似乎没有显著的相互作用。使用阿片受体亚型特异性激动剂（分别对μ、δ和κ受体特异的DAMGO、DPDPE和U-50488H）的研究表明，阿片肽对肾小球带的作用似乎仅由μ受体介导，而内层带细胞的反应由μ受体介导，并且在较小程度上由κ受体介导。最后，对由阿片肽和受体激动剂激活的第二信使系统的研究表明，这些肽的作用是增加肌醇三磷酸的标记，并强烈表明，在大鼠肾上腺皮质中，μ和κ阿片受体均与磷脂酶C的激活有关。
