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.

The kallikrein‐kinin system, angiotensin converting enzyme inhibitors and insulin sensitivity

“…Parallel results have been obtained in obese Zucker rats [29,69]. Rett et al [70] have observed that BK through the activation of B 2 receptor stimulated glucose transport in rat heart and a cross-talk between the insulin receptor and the bradykinin pathway has been suggested in rat cardiomyocytes [67]. However, NO and cGMP inhibit myocardial glucose uptake [71,72], while NO increases insulin sensitivity in the whole organism as demonstrated by the effects of NO synthase inhibitors or the results obtained in mice with gene disruption of nitric oxide synthase [73].…”

“…This action of BK is mediated by inhibition of protein tyrosine phosphatases [65] (Figure 2). On the other hand, insulin increased the formation of IP3 induced by BK in rat skeletal myoblasts [66] and in rat cardiomyocytes [67].…”

Potentiation of bradykinin actions by analogues of the bradykinin potentiating nonapeptide BPP9α

“…Bradykinin potentiating factors can influence both desensitization and resensitization, as well as the hetero-oligomerization of the B 2 receptor including the interaction with ACE [54] and other degrading enzymes [15]. At the level of signal pathways, a crosstalk with other pathways induced by other hormones [43] or nonreceptormediated intracellular reactions [28] have been observed.…”

Bradykinin‐mediated Ca2+ signalling regulates cell growth and mobility in human cardiac c‐Kit+ progenitor cells

“…In bovine coronary artery, bradykinin‐induced vasodilation is related to endothelial ${\mathrm{Ca}}_{\mathrm{normali}}^{2+}$ increase mediated by cyclic ADP ribose‐RyRs Ca 2+ signalling pathway, but not PLC‐IP3Rs Ca 2+ signalling pathway, because the PLC inhibitor U73122 and the IP3R inhibitor 2‐aminoethoxydiphenyl borate do not affect the ${\mathrm{Ca}}_{\mathrm{normali}}^{2+}$ increase induced by bradykinin 41. However, an earlier study demonstrated that bradykinin induces an increase in inositol 1,4,5‐triphosphate (IP3) in neonatal rat cardiomyocytes42 and bradykinin‐mediated short nocifensive responses is related to activating PLC, followed by Orai1 in afferent sensory neurons 18…”