Changes in inositol lipids and phosphates after stimulation of the MAS-transfected NG115-401L-C3 cell line by mitogenic and non-mitogenic stimuli.
A neuronal cell line (NG115-401L-C3) was stimulated by mitogenic (angiotensin) and non-mitogenic (bradykinin) peptides and examined for the time course of changes in the levels of radiolabelled inositol phosphates and phospholipids. Both peptides stimulated the time-dependent production of Ins(1,4,5)P3 and related metabolites. Bradykinin caused a much larger increase in Ins(1,4,5)P3 than did angiotensin. However, both peptides stimulated similar rises in the levels of Ins(1,3,4)P3 and InsP4. Bradykinin, but not angiotensin, caused a rapid (within 2 s) fall in the levels of PtdIns(4,5)P2 and PtdIns(4)P. Serum pretreatment of the cells caused a 2-3-fold potentiation of both the responses to bradykinin and angiotensin. Although significant levels of PtdIns(3)P were detected in resting cells, neither mitogenic (angiotensin, insulin-like growth factor I, transforming growth factor beta) nor non-mitogenic (bradykinin, nerve growth factor, interleukin-1) receptor activation changed its levels, arguing against regulation of either PtdIns 3-kinase or PtdIns(3)P phosphatase. We conclude that, as judged by the levels of its product. PtdIns(3)P, the enzyme PtdIns 3-kinase is not activated. This questions the significance of this activity in the receptor-mediated initiation of DNA synthesis.
Poyner
D R
DR
M.R.C. Molecular Neurobiology Unit, M.R.C. Centre, Cambridge.
Hawkins
P T
PT
Benton
H P
HP
Hanley
M R
MR
D000804:Angiotensin II / Q000494:pharmacology*; D001920:Bradykinin / Q000494:pharmacology*; D002460:Cell Line / Q000378:metabolism / Q000502:physiology; D016207:Cytokines / Q000494:pharmacology / Q000502:physiology; D004247:DNA / Q000096:biosynthesis; D006133:Growth Substances / Q000494:pharmacology / Q000502:physiology; D007290:Inosine Diphosphate / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism*; D007700:Kinetics; D008934:Mitogens / Q000494:pharmacology*; D009447:Neuroblastoma / Q000235:genetics / Q000473:pathology; D010743:Phospholipids / Q000378:metabolism*; D011945:Receptors, Angiotensin / Q000378:metabolism; D013268:Stimulation, Chemical; D014162:Transfection; D010738:Type C Phospholipases / Q000378:metabolism
D016207:Cytokines; D006133:Growth Substances; D007295:Inositol Phosphates; D008934:Mitogens; D010743:Phospholipids; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D007290:Inosine Diphosphate; D004247:DNA; D010738:Type C Phospholipases; D001920:Bradykinin