Receptor coupled events in bradykinin action: rapid production of inositol phosphates and regulation of cytosolic free Ca2+ in a neural cell line.
The addition of bradykinin to NG115-401L cells grown on coverslips results in the generation of rapid transient increases in intracellular [Ca2+] and inositol phosphates. Changes in intracellular Ca2+, measured using the fluorescent indicator dye Fura-2, show two components; an initial rapid peak in [Ca2+]i which is essentially independent of extracellular Ca2+, and a sustained plateau dependent on the presence of extracellular Ca2+. Analysis of bradykinin stimulated production of [3H]inositol phosphates, by h.p.l.c., shows a rapid biphasic production of inositol 1,4,5-trisphosphate, inositol tetrakisphosphate and inositol bisphosphates, followed by a sustained rise in inositol 1,3,4-trisphosphate production. Quantitative measurements have indicated the presence of other, more polar, [3H]inositol-labelled metabolites which do not show major changes on bradykinin stimulation. The initial phase of inositol phosphate production parallels the rapid transient increase in intracellular [Ca2+], however, the second phase of inositol phosphate production occurs when intracellular [Ca2+] is declining and implies a complex series of regulatory events following receptor stimulation. Similar time courses of inositol 1,4,5-trisphosphate and Ca2+ signals provides supporting evidence that inositol 1,4,5-trisphosphate is the second messenger coupling bradykinin receptor stimulation to release of Ca2+ from intracellular stores.
D000818:Animals; D001920:Bradykinin / Q000378:metabolism / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D005910:Glioma; D007295:Inositol Phosphates / Q000096:biosynthesis*; D007700:Kinetics; D009447:Neuroblastoma; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D013403:Sugar Phosphates / Q000096:biosynthesis*
D007295:Inositol Phosphates; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter; D013403:Sugar Phosphates; D001920:Bradykinin; D002118:Calcium