Retinoic acid treatment enhances the acetylcholine contents in the human teratocarcinoma cell line NTera-2.
Human NTera-2/clone D1 teratocarcinoma cells are induced by retinoic acid (RA) to differentiate into postmitotic cells with morphological and biochemical characteristics of embryonic human neurones. Currently only limited information concerning peptide-contents and neurotransmitter pools of these cells is available. Zeller and Strauss [Int. J. Dev. Neurosci. 1995;13(5):437] described an increase in choline acetyltransferase (ChAT) activity in RA-treated, but not in untreated NTera-2 cells, suggesting the induction of a cholinergic phenotype during treatment with RA. In the present study we investigated the effect of RA-differentiation on the amount of the neurotransmitters acetylcholine (ACh), and dopamine in NTera-2 in order to specify the transmitter phenotype induced by RA-differentiation. We found that a 4-week treatment of NTera-2 cells with 10 microM RA markedly increased the ACh-content of these cells, while dopamine levels were unchanged. Depolarisation with potassium (60 mM) enhanced ACh-outflow in the differentiated cells in a Ca(++) dependent way. Also neuropeptides like substance P and NPY were detectable in the undifferentiated NTera-2 cells, while vasointestinal peptide (VIP) could not be found in either precursor or RA-differentiated cells. Differentiation was accompanied by a marked reduction of neutral endopeptidase enzyme activity and aminopeptidase activity. From these observations it was concluded that RA induces a cholinergic neurochemical differentiation of this human teratocarcinoma cell line, and that these cells might provide a model system to investigate cholinergic properties of human origin.
Fischer
H S
HS
Division of Neurochemistry, Department of Psychiatry, University Hospital Innsbruck, Anichstrasse 35, A-6020, Innsbruck, Austria.
Berti
I
I
Schatz
D S
DS
Humpel
C
C
Saria
A
A
D000109:Acetylcholine / Q000378:metabolism*; D018826:CD13 Antigens / Q000378:metabolism; D002118:Calcium / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism; D006801:Humans; D015260:Neprilysin / Q000378:metabolism; D009478:Neuropeptide Y / Q000378:metabolism; D010641:Phenotype; D011189:Potassium Chloride / Q000494:pharmacology; D013373:Substance P / Q000378:metabolism; D018243:Teratocarcinoma / Q000378:metabolism* / Q000473:pathology; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism
D009478:Neuropeptide Y; D013373:Substance P; D014660:Vasoactive Intestinal Peptide; D014212:Tretinoin; D011189:Potassium Chloride; D018826:CD13 Antigens; D015260:Neprilysin; D000109:Acetylcholine; D002118:Calcium; D004298:Dopamine