Lithium dramatically potentiates neurotensin/neuromedin N gene expression.
Lithium perturbs intracellular signal transduction pathways used by neurotransmitters, suggesting that changes in receptor signalling may underlie its actions in the treatment of manic depressive illness. Little attention, however, has been directed toward possible additional actions at the level of specific gene expression, particularly of genes encoding neurotransmitters or neuromodulators. In PC12 pheochromocytoma cells, lithium dramatically potentiates increases in intracellular levels of the neuropeptide neurotensin and the mRNA encoding it, caused by combinations of nerve growth factor, dexamethasone, and the adenylate cyclase activator, forskolin. This result demonstrates that lithium can profoundly influence the expression of a specific neuropeptide gene in a previously unanticipated manner and suggests that changes in gene expression might be involved in its therapeutic activity.
Dobner
P R
PR
Department of Molecular Genetics and Microbiology, University of Massachusetts Medical Center, Worcester 01655.
Tischler
A S
AS
Lee
Y C
YC
Bloom
S R
SR
Donahue
S R
SR
D000310:Adrenal Gland Neoplasms; D000818:Animals; D002460:Cell Line; D002712:Chlorides / Q000494:pharmacology*; D005576:Colforsin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D005796:Genes / Q000187:drug effects*; D007700:Kinetics; D008094:Lithium / Q000494:pharmacology*; D018021:Lithium Chloride; D009414:Nerve Growth Factors / Q000494:pharmacology; D009496:Neurotensin / Q000235:genetics*; D010446:Peptide Fragments / Q000235:genetics*; D010673:Pheochromocytoma; D014158:Transcription, Genetic / Q000187:drug effects*
D002712:Chlorides; D009414:Nerve Growth Factors; D010446:Peptide Fragments; C042090:neuromedin N; D005576:Colforsin; D009496:Neurotensin; D003907:Dexamethasone; D008094:Lithium; D018021:Lithium Chloride