Effects of short- and long-term exposure to c-AMP and c-GMP on the noradrenaline transporter

• Published in: Neuropharmacology Vol. 40; no. 4; pp. 607 - 617
• Main Authors: Bryan-Lluka, Lesley J., Paczkowski, Filip A., Bönisch, Heinz
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.03.2001; Elsevier
• Subjects: 8-Bromo Cyclic Adenosine Monophosphate - pharmacology; Animals; Biological and medical sciences; Biological Transport - drug effects; Bucladesine - pharmacology; c-AMP; c-GMP; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cell physiology; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Cholera Toxin - pharmacology; Colforsin - pharmacology; COS Cells; Cyclic AMP - metabolism; Cyclic GMP - metabolism; Fundamental and applied biological sciences. Psychology; Human SK-N-SH-SY5Y cells; Humans; Membrane and intracellular transports; Molecular and cellular biology; Noradrenaline transporter; Norepinephrine - pharmacokinetics; Norepinephrine Plasma Membrane Transport Proteins; PC12 Cells; Rat PC12 cells; Rats; Regulation; RNA, Messenger - drug effects; RNA, Messenger - genetics; RNA, Messenger - metabolism; Staurosporine - pharmacology; Symporters; Time Factors; Tumor Cells, Cultured; Vertebrates: nervous system and sense organs; Rat PC12 cells; c-GMP; c-AMP; Regulation; Human SK-N-SH-SY5Y cells; Noradrenaline transporter; Short term; Human; Rat; Biological transport; Rodentia; Cyclic AMP; 3',5'-GMP; Catecholamine; Gene expression; In vitro; Long term; Conveyor; Signal transduction; Vertebrata; Mammalia; Animal; Established cell line; Genetics; Norepinephrine; Mechanism of action
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/S0028-3908(00)00201-X

The effects of short- and long-term exposure of cells to elevated cyclic adenosine monophosphate (c-AMP), using dibutyryl-c-AMP, 8-bromo-c-AMP, cholera toxin or forskolin, or cyclic guanosine monophosphate (c-GMP), using dibutyryl-c-GMP or 8-bromo-c-GMP, on the activity and expression of the noradrenaline transporter (NAT) were examined. Short- or long-term c-GMP elevation had no effects on 3H-noradrenaline uptake by rat PC12 phaeochromocytoma cells or human SK-N-SH-SY5Y neuroblastoma cells. Short-term c-AMP elevation (for 17 min experiment duration) caused a decrease in 3H-noradrenaline uptake by PC12 cells, but had no effects on SK-N-SH-SY5Y cells or COS-7 cells transfected with human or rat NAT cDNA. c-AMP did not affect 3H-nisoxetine binding to PC12 cells. Long-term (24 h) exposure to elevated c-AMP levels caused a decrease in 3H-noradrenaline uptake and NAT mRNA in PC12 cells, but had no effects on SK-N-SH-SY5Y cells and caused a small increase in 3H-noradrenaline uptake in COS-7 cells heterologously expressing rat or human NAT. Hence, c-AMP, but not c-GMP, causes a cell type-dependent reduction in NAT activity after short-term exposure and a reduction in NAT expression after long-term exposure.