Activin A stimulates catecholamine secretion from rat adrenal chromaffin cells: a new physiological mechanism

Abstract

Activin A is a member of the transforming growth factorfamily 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 EC 50 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 Ca 2+ channels were blocked by Cd 2+ (200 µM). We conclude from these findings that activin A is capable of stimulating a robust level of catecholamine secretion from adrenal chromaffin cells in a concentrationdependent manner. This occurs via the opening of voltage-gated Ca 2+ channels, causing Ca 2+ 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.

Phosphatidylinositol(4,5)bisphosphate coordinates actin-mediated mobilization and translocation of secretory vesicles to the plasma membrane of chromaffin cells

“…Consistent with our findings, expression of PI4P5K Iα has also been shown to induce actin remodelling in COS-7 cells 43 . Hypertonic stress, which increases PtdIns(4,5)P 2 levels by activating PI4P5K Iβ, also produces actin polymerization and reorganization 44 . Our finding that 20 ± 1% of vesicles translocate to the plasma membrane from outside the evanescent field following IC87114 treatment, and that vesicles undergoing translocation and transient docking exhibit a directed motion consistent with transport along F-actin, support a growing body of evidence highlighting the role of actin filaments in guiding LDCVs to release sites 3,35 .…”

“…The isolated chromaffin cells 44,45 were either directly used for lipid analysis or cultured in Dulbecco's modified Eagle's Medium supplemented with 1% penicillin/streptomycin (Invitrogen) and 10% fetal calf serum (JRH Biosciences) and plated on tissue culture dishes (35 mm, Nunclon) for 3-4 days before experiments.…”

Localisation and Role of Activin Receptor‐Interacting Protein 1 in Mouse Brain

“…Activin A is widely produced and plays important roles in various tissues , such as in hypothalamic neuroendocrinological and feeding‐related systems, as well as in cortical and limbic pathways, as a neuromodulator or for maintenance of neurones . Activin receptors are transmembrane proteins, have the serine/threonine kinase domain in their cytoplasmic regions and are widely distributed in various tissues.…”