Inhibition of bradykinin-induced cytosolic Ca2+ elevation by muscarinic stimulation without attenuation of inositol 1,4,5-trisphosphate production in human neuroblastoma SK-N-BE(2)C cells.
Cross talk between two phospholipase C (PLC)-linked receptor signalings was investigated in SK-N-BE(2)C human neuroblastoma cells. Sequential stimulation with two agonists at 5-min intervals was performed to examine the interaction between muscarinic and bradykinin (BK) receptors. Pretreatment of cells with a maximal effective concentration (5 microM) of BK did not affect the subsequent carbachol (CCh)-induced [Ca2+]i rise, but CCh (1 mM) pretreatment completely abolished the BK-induced [Ca2+]i rise without inhibition of BK-induced inositol 1,4,5-trisphosphate (IP3) generation. Thapsigargin (1 microM) pretreatment abolished the subsequent BK- and CCh-induced [Ca2+]i rise, though it did not affect agonist-induced IP3 generation. However, the addition of atropine at plateau phases of CCh-induced [Ca2+]i rise and IP3 production caused a rapid decline to the basal levels and then restored the [Ca2+]i rise by BK. Treatment of cells with both CCh and BK at the same time showed additive effects in IP3 production. However, the [Ca2+]i rise induced by both agonists in the presence or absence of extracellular Ca2+ was the same as the responses triggered by CCh alone. The results suggest that each receptor or receptor-linked PLC activity is not influenced by pretreatment with the other agonist but IP3-sensitive Ca2+ stores are shared by signal pathways from both receptors.
Suh
B C
BC
Department of Life Science, Pohang University of Science and Technology, Republic of Korea.
Kim
K T
KT
D001920:Bradykinin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism*; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis*; D007425:Intracellular Membranes / Q000378:metabolism; D009116:Muscarine / Q000378:metabolism*; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology; D009994:Osmolar Concentration; D018002:Receptors, Bradykinin / Q000502:physiology; D011976:Receptors, Muscarinic / Q000502:physiology; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D018002:Receptors, Bradykinin; D011976:Receptors, Muscarinic; D009116:Muscarine; D015544:Inositol 1,4,5-Trisphosphate; D002217:Carbachol; D001920:Bradykinin; D002118:Calcium