Effect of apomorphine, alpha-methylparatyrosine, haloperidol and reserpine on DOPA production in clonal cell lines (PC-12 and N1E-115).
The effect of various drugs on DOPA production in the pheochromocytoma clone PC-12 and the neuroblastoma clone N1E-115 was studied. The N1E-115 cells contain only very low amounts of dopamine due to a lack of the aromatic L-amino acid decarboxylase, whereas the PC-12 cells are rich in dopamine. alpha-Methyl-p-tyrosine and apomorphine blocked DOPA production in both cell clones. Reserpine and haloperidol reduced the intracellular dopamine in the PC-12 cells and simultaneously induced a blockade of cellular DOPA production. The released dopamine was primarily recovered as 3,4-dihydroxyphenylacetic acid indicating a release of dopamine into the cytoplasm. This transient increase of cytoplasmic dopamine by reserpine or haloperidol brings about the inhibition of DOPA production in the PC-12 cells. Our results show that the PC-12 clone especially reacts to various drugs like other in vitro systems and may serve as an additional model for studying drug effects on catecholamine biosynthesis and metabolism.
D000310:Adrenal Gland Neoplasms / Q000378:metabolism; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D002460:Cell Line; D004295:Dihydroxyphenylalanine / Q000096:biosynthesis*; D004298:Dopamine / Q000378:metabolism; D006220:Haloperidol / Q000494:pharmacology*; D008781:Methyltyrosines / Q000494:pharmacology*; D009447:Neuroblastoma / Q000378:metabolism; D010673:Pheochromocytoma / Q000378:metabolism; D051381:Rats; D012110:Reserpine / Q000494:pharmacology*; D019805:alpha-Methyltyrosine
D008781:Methyltyrosines; D004295:Dihydroxyphenylalanine; D019805:alpha-Methyltyrosine; D012110:Reserpine; D006220:Haloperidol; D001058:Apomorphine; D004298:Dopamine