The effects of beta-phorbol-12,13 dibutyrate on agonist-induced increases in [Ca2+]i in N1E-115 cells. Differential modulation of responses to angiotensin II and bradykinin.
Addition of angiotensin II (A2; 500 nM) to populations of fura-2-loaded N1E-115 cells resulted in a transient increase in intracellular calcium which was abolished by pre-treatment with the phorbol ester, beta-phorbol-12,13 dibutyrate (PDBu) (1.5 microM). The inhibitory effects were reversed by the protein kinase C inhibitor, staurosporine (150 nM), and down-regulation of protein kinase C was observed over 48 hr. Responses to maximally effective concentrations of histamine (300 microM), ATP (100 microM), UTP (100 microM) and carbachol (100 microM) were similarly inhibited by phorbol pre-treatment but the response to bradykinin (BK) (100 nM) was unaffected. When the concentrations of BK and A2 were adjusted to produce the same-sized calcium signals, PDBu pre-treatment abolished the response to A2 but only partially inhibited the response to BK. From the data presented here we can conclude that the calcium response to BK in N1E-115 cells is less susceptible to the inhibitory effects of protein kinase C activation than the response produced by A2.
Iredale
P A
PA
Department of Physiology and Pharmacology, Medical School, Queen's Medical Centre, Nottingham, U.K.
Martin
K F
KF
Hill
S J
SJ
Kendall
D A
DA
D000470:Alkaloids / Q000494:pharmacology; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D015536:Down-Regulation; D004789:Enzyme Activation / Q000187:drug effects; D051379:Mice; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D019311:Staurosporine; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000470:Alkaloids; D000804:Angiotensin II; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C; D019311:Staurosporine; D001920:Bradykinin; D002118:Calcium