Keating Damien J, Chen Chen
Prince Henry's Institute of Medical Research, Clayton, Australia.
J Endocrinol. 2005 Aug;186(2):R1-5. doi: 10.1677/joe.1.06301.
Activin A is a member of the transforming growth factor-beta family and has known roles in the adrenal cortex, from which activin A is secreted. We aimed to find whether activin A induces secretion of catecholamines from chromaffin cells of the adrenal medulla, which neighbours the adrenal cortex in vivo. Using carbon fibre amperometry, we were able to measure catecholamine secretion in real-time from single chromaffin cells dissociated from the rat adrenal medulla. Activin A stimulated catecholamine secretion in a rapid and dose-dependent manner from chromaffin cells. This effect was fully reversible upon washout of activin A. The minimum dose at which activin A had a maximal effect was 2 nM, with an EC50 of 1.1 nM. The degree of secretion induced by activin A (2 nM) was smaller than that due to membrane depolarization caused by an increase in the external K+ concentration from 5 to 70 mM. No response to activin A was seen when Ca2+ channels were blocked by Cd2+ (200 microM). We conclude from these findings that activin A is capable of stimulating a robust level of catecholamine secretion from adrenal chromaffin cells in a concentration-dependent manner. This occurs via the opening of voltage-gated Ca2+ channels, causing Ca2+ entry, thereby triggering exocytosis. These findings illustrate a new physiological role of activin A and a new mechanism in the control of catecholamine secretion from the adrenal medulla.
激活素A是转化生长因子-β家族的成员，在其分泌部位肾上腺皮质中发挥已知作用。我们旨在探究激活素A是否能诱导与肾上腺皮质在体内相邻的肾上腺髓质嗜铬细胞分泌儿茶酚胺。利用碳纤维安培法，我们能够实时测量从大鼠肾上腺髓质分离出的单个嗜铬细胞的儿茶酚胺分泌情况。激活素A能以快速且剂量依赖性的方式刺激嗜铬细胞分泌儿茶酚胺。在洗脱激活素A后，这种效应完全可逆。激活素A产生最大效应的最小剂量为2 nM，半数有效浓度（EC50）为1.1 nM。激活素A（2 nM）诱导的分泌程度小于细胞外K⁺浓度从5 mM增加到70 mM引起的膜去极化所导致的分泌程度。当Ca²⁺通道被Cd²⁺（200 μM）阻断时，未观察到对激活素A的反应。从这些发现中我们得出结论，激活素A能够以浓度依赖性方式刺激肾上腺嗜铬细胞分泌大量儿茶酚胺。这是通过电压门控Ca²⁺通道的开放，导致Ca²⁺内流，从而触发胞吐作用实现的。这些发现阐明了激活素A的一种新的生理作用以及肾上腺髓质儿茶酚胺分泌调控的一种新机制。
