Neurite outgrowth in PC12 cells is enhanced by guanosine through both cAMP-dependent and -independent mechanisms.
Extracellular guanosine, guanosine triphosphate (GTP), and 5'-N'-ethylcarboxamidoadenosine (NECA), each significantly enhanced the proportion of nerve growth factor (NGF)-treated rat pheochromocytoma (PC12) cells which had neurites, greater than that in cultures exposed to NGF alone. Guanosine and NECA, but not GTP, increased intracellular cAMP concentrations. An adenylate cyclase inhibitor, SQ22536, completely blocked the cAMP increase induced by both guanosine and 0.1 microM NECA. However, SQ22536 only partially blocked guanosine enhanced neurite outgrowth, although it completely blocked the neuritogenic effect of NECA. Therefore guanosine-enhanced neurite outgrowth through both cAMP-dependent and -independent mechanisms, while the effect of GTP was cAMP-independent.
Gysbers
J W
JW
Department of Biomedical Sciences, Health Sciences Centre, McMaster University, Hamilton, Ontario, Canada. gysbersjohn@freenet.hamilton.on.ca
Rathbone
M P
MP
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006151:Guanosine / Q000494:pharmacology*; D006160:Guanosine Triphosphate / Q000502:physiology; D009414:Nerve Growth Factors / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D016716:PC12 Cells; D051381:Rats
D000067956:Adenylyl Cyclase Inhibitors; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D009414:Nerve Growth Factors; D006151:Guanosine; C017759:9-(tetrahydro-2-furyl)-adenine; D005576:Colforsin; D019830:Adenosine-5'-(N-ethylcarboxamide); D006160:Guanosine Triphosphate; D000242:Cyclic AMP; D000225:Adenine; D000241:Adenosine