title: Insulin potentiates bradykinin-induced inositol 1,4,5-triphosphate in neonatal rat cardiomyocytes.
abstract: This study investigated whether cross-talk between insulin and the bradykinin receptor exists to modulate bradykinin-induced increase in inositol 1,4,5-triphosphate (IP3) in neonatal rat cardiomyocytes. Treatment of the cultures with 1, 2, and 20 nM of insulin for 90 min before adding bradykinin increased the IP3 response to the same bradykinin dose to 372.0 +/- 17.8, 413.7 +/- 17.7, and 457.3 +/- 18.2 pmol/mg protein, respectively. Tyrphostine A23 and genistein (tyrosine kinase inhibitors) decreased the bradykinin (10 nM)-induced IP3 production potentiated by 2 nM insulin from 400.7 +/- 19.4 pmol/mg protein to 297.3 +/- 42.4 and 314.3 +/- 37.5 pmol/mg protein, respectively. Administration of 100 nM N-(6-aminohexyl)-5-chloro-naphthalenesulfonamide (W7, a calmodulin antagonist) significantly increased the bradykinin (10 nM)-induced IP3 production from 311.7 +/- 13.0 pmol/mg protein in the absence of insulin to 457.8 +/- 19.9, 578.2 +/- 25.9, and 665.2 +/- 16.0 pmol/mg protein in the presence of 1, 2, and 20 nM insulin, respectively. These results demonstrate that cross-talk between the insulin receptor and the bradykinin signaling system may exist in neonatal rat cardiomyocytes. Tyrosine kinase appears to play an important role in the cross-talking. Calmodulin controls the IP3 response to bradykinin by a negative feedback mechanism.
authors.affiliation: Department of Anesthesiology, University of Hirosaki School of Medicine, Hirosaki National Hospital, Aomori, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Kudoh
authors.forename: Emiko
authors.initials: E
authors.lastname: Kudoh
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Katagai
authors.forename: Tomoko
authors.initials: T
authors.lastname: Takazawa
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001920:Bradykinin / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis*; D007328:Insulin / Q000494:pharmacology*; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D018002:Receptors, Bradykinin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D007328:Insulin; D018002:Receptors, Bradykinin; D015544:Inositol 1,4,5-Trisphosphate; D011505:Protein-Tyrosine Kinases; D001920:Bradykinin