Bradykinin-induced inositol 1,4,5-triphosphate in neonatal rat cardiomyocytes is activated by endotoxin.
We studied the effect of endotoxin on bradykinin-induced inositol 1,4,5-triphosphate (IP3) production and the relationship between IP3 and phospholipase A2 or thromboxane A2. When exposed with 0.1, 1.0, and 10 microg ml(-1) lipopolysaccharide (LPS) for short-term (60 min), 100 nmol L(-1) bradykinin-induced IP3 production was stimulated in a dose-dependent manner from 569.2+/-42.4 in absence of LPS to 714.3+/-52.8, 804.5+/-42.6, and 894.1+/-62.6 pmol mg protein(-1). Treatment of 100 micromol L(-1) ACA (a phospholipase A2 inhibitor) and 10 micromol L(-1) BM13.177 (a thromboxane A2 inhibitor) significantly decreased bradykinin-induced IP3 production and LPS (1.0 microg mL(-1)) modulation of bradykinin-induced IP3 formation from 804.5+/-42.6 to 217.4+/-12.7 and 208.6+/-17.1 pmol mg protein(-1), respectively. LPS modulation of bradykinin-induced IP3 production was significantly blocked by 1 micromol L(-1) TMB-8 (an intracellular Ca2+ antagonist) from 804.5+/-42.6 to 507.8+/-33.4 pmol mg protein(-1). LPS modulation of bradykinin-induced IP3 production was significantly inhibited from 804.5+/-42.6 to 397.4+/-30.3 pmol mg protein(-1) by treatment of 10 micromol L(-1) indomethacin. In conclusion, short-term administration of LPS stimulates bradykinin-induced IP3 formation through activation of phospholipase A2 and thromboxane A2 and the stimulation is associated with an elevation of intracellular Ca2+.
Kudoh
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Department of Anesthesiology, University of Hirosaki School of Medicine, Japan.
Matsuki
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D000818:Animals; D000831:Animals, Newborn; D001920:Bradykinin / Q000494:pharmacology*; D002934:Cinnamates / Q000494:pharmacology; D004731:Endotoxins / Q000633:toxicity*; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis*; D007700:Kinetics; D008070:Lipopolysaccharides / Q000633:toxicity; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D013449:Sulfonamides / Q000494:pharmacology; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors; D062367:ortho-Aminobenzoates / Q000494:pharmacology
D002934:Cinnamates; D004731:Endotoxins; D008070:Lipopolysaccharides; D013449:Sulfonamides; D062367:ortho-Aminobenzoates; C085901:4-amylcinnamoylanthranilic acid; D013928:Thromboxane A2; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; C040624:sulotroban; D015544:Inositol 1,4,5-Trisphosphate; D001920:Bradykinin; D007213:Indomethacin