NEURITE OUTGROWTH IN PC12 CELLS IS ENHANCED BY GUANOSINE THROUGH BOTHCAMP-DEPENDENT AND CAMP-INDEPENDENT MECHANISMS

Extracellular guanosine, guanosine triphosphate (GTP), and 5'-N'-ethyl carboxamidoadenosine (NECA), each significantly enhanced the proportio n of nerve growth factor (NGF)-treated rat pheochromocytoma (PC12) cel ls which had neurites, greater than that in cultures exposed to NGF al one. Guanosine and NECA, but not GTP, increased intracellular cAMP con centrations. An adenylate cyclase inhibitor, SQ22536,completely blocke d the cAMP increase induced by both guanosine and 0.1 mu M NECA, Howev er, SQ22536 only partially blocked guanosine enhanced neurite outgrowt h, although it completely blocked the neuritogenic effect of NECA. The refore guanosine-enhanced neurite outgrowth through both cAMP-dependen t and -independent mechanisms, while the effect of GTP was cAMP-indepe ndent. (C) 1996 Elsevier Science Ireland Ltd.