Regulation of corticotropin-releasing factor secretion and synthesis in the human neuroblastoma clones- BE(2)-M17 and BE(2)-C.
The BE(2)-M17 and BE(2)-C human neuroblastoma cell lines have been shown to synthesize and secrete corticotropin-releasing factor (CRF) following retinoic acid treatment. It has been demonstrated that CRF secretion and intracellular synthesis increases in response to forskolin treatment. In this report, we have further characterized these cells in response to protein kinase C activators, dexamethasone, interleukin-1 alpha, as well as various neurotransmitters and peptides. Nanomolar concentrations of the phorbol ester--phorbol 12 myristate 13--acetate (TPA), increased intracellular CRF content in both cell lines while increasing secretion only in the BE(2)-M17 cell. Nanomolar concentrations of dexamethasone were not able to alter basal levels of secretion and content in either cell type. However, in the BE(2)-M17 cell but not the BE(2)-C cell, the same concentrations of dexamethasone added to 30 microM forskolin augmented levels of CRF secretion and content. Likewise, the same augmented response in CRF secretion and content was seen only in the BE(2)-M17 cell line when nanomolar concentrations of dexamethasone were added to 20 nM TPA. Furthermore, only in the BE(2)-M17 cell line were micromolar levels of the biogenic amine serotonin able to increase levels of CRF secretion and content. No effects on CRF in both cell lines were demonstrable with picomolar levels of interleukin-1 alpha as well as micromolar levels of acetylcholine, norepinephrine, arginine-vasopressin, oxytocin, and angiotensin-II. The potential usefulness of these cells as models of central nervous system or placental CRF-containing neurons is discussed.
Kasckow
J W
JW
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA.
Han
J H
JH
Parkes
D G
DG
Mulchahey
J J
JJ
Owens
M J
MJ
Risby
E D
ED
Fisher
J
J
Nemeroff
C B
CB
D005576:Colforsin / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000096:biosynthesis* / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D009447:Neuroblastoma / Q000378:metabolism*; D009479:Neuropeptides / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D007375:Interleukin-1; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D005576:Colforsin; D012701:Serotonin; D003907:Dexamethasone; D003346:Corticotropin-Releasing Hormone; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate