Mazzocchi G, Malendowicz L K, Andreis P G, Meneghelli V, Markowska A, Belloni A S, Nussdorfer G G
Department of Anatomy, University of Padua, Italy.
Brain Res. 1994 Oct 24;661(1-2):91-6. doi: 10.1016/0006-8993(94)91185-1.
Neuropeptide K (NPK), a member of the kassinin-like tachykinin family, is contained in the rat hypothalamus and is known to stimulate pituitary ACTH release. The intraperitoneal bolus administration of NPK dose-dependently enhanced corticosterone blood level not only in intact rats, but also in hypophysectomized/ACTH replaced animals. NPK did not affect corticosterone secretion of dispersed rat adrenocortical cells; however, it concentration-dependently raised basal corticosterone production by decapsulated adrenal quarters (including both cortical and medullary tissues). Minimal and maximal effective concentrations were 10(-9) and 10(-8) M, respectively. 10(-8) M NPK potentiated corticosterone response of adrenal quarters elicited by 10(-12) M ACTH, but not that evoked by higher concentrations of ACTH. The direct corticosterone secretagogue effect of 10(-8) M NPK is annulled by 10(-6) M alpha-helical-CRH or corticotropin-inhibiting peptide, competitive inhibitors of CRH and ACTH, respectively. In light of these findings, the hypothesis is advanced that NPK exerts a direct stimulatory action on adrenocortical secretion and that the mechanism underlying this effect of NPK may involve the activation of the intra-medullary CRH/ACTH system.
神经肽K（NPK）是类速激肽家族中似铃蟾肽的成员之一，存在于大鼠下丘脑，已知可刺激垂体促肾上腺皮质激素（ACTH）释放。腹腔推注NPK不仅在完整大鼠中，而且在垂体切除/ACTH替代的动物中，均剂量依赖性地提高了血液中皮质酮水平。NPK不影响分散的大鼠肾上腺皮质细胞的皮质酮分泌；然而，它能浓度依赖性地提高摘除被膜的肾上腺组织块（包括皮质和髓质组织）的基础皮质酮生成。最小和最大有效浓度分别为10^(-9)和10^(-8)M。10^(-8)M NPK增强了由10^(-12)M ACTH引起的肾上腺组织块的皮质酮反应，但不增强由更高浓度ACTH引起的反应。10^(-6)M的α-螺旋促肾上腺皮质激素释放激素（CRH）或促肾上腺皮质激素抑制肽（分别为CRH和ACTH的竞争性抑制剂）可消除10^(-8)M NPK的直接皮质酮促分泌作用。根据这些发现，提出了如下假说：NPK对肾上腺皮质分泌具有直接刺激作用，且NPK这一作用的潜在机制可能涉及髓内CRH/ACTH系统的激活。
