BDNF stimulates Ca2+ oscillation frequency in melanotrope cells of Xenopus laevis: contribution of IP3-receptor-mediated release of intracellular Ca2+ to gene expression.
Pituitary melanotrope cells of the amphibian Xenopus laevis are neuroendocrine cells regulating the animal's skin color adaptation through secretion of α-melanophore-stimulating hormone (α-MSH). To fulfill this function optimally, the melanotrope cell undergoes plastic changes in structure and secretory activity in response to changed background light conditions. Xenopus melanotrope cells display Ca(2+) oscillations that are thought to drive α-MSH secretion and gene expression. They also produce brain-derived neurotrophic factor (BDNF), which stimulates in an autocrine way the biosynthesis of the α-MSH precursor, pro-opiomelanocortin (POMC). We have used this physiological adaptation mechanism as a model to investigate the role of BDNF in the regulation of Ca(2+) kinetics and Ca(2+)-dependent gene expression. By dynamic video imaging of isolated cultured melanotropes we demonstrated that BDNF caused a dose-dependent increase in Ca(2+) oscillation frequency up to 64.7±2.3% of control level. BDNF also induced a transient Ca(2+) peak in Ca(2+)-free medium, which was absent when calcium stores were blocked by thapsigargin and 2-aminoethoxydiphenyl borate, indicating that BDNF stimulates acute release of Ca(2+) from IP(3)-sensitive intracellular Ca(2+) stores. Moreover, we show that thapsigargin inhibits the expression of BDNF transcript IV (by 61.1±28.8%) but does not affect POMC transcript. We conclude that BDNF mobilizes Ca(2+) from IP(3)-sensitive intracellular Ca(2+) stores and propose the possibility that the resulting Ca(2+) oscillations selectively stimulate expression of the BDNF gene.
Kuribara
Miyuki
M
Department of Cellular Animal Physiology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, Nijmegen, The Netherlands.
Eijsink
Vivian D
VD
Roubos
Eric W
EW
Jenks
Bruce G
BG
Scheenen
Wim J J M
WJ
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism*; D052717:Melanotrophs / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D055099:Neuroendocrine Cells / Q000187:drug effects* / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014982:Xenopus laevis
D019208:Brain-Derived Neurotrophic Factor; D053496:Inositol 1,4,5-Trisphosphate Receptors; D002118:Calcium