Sympathoexcitation by bradykinin involves Ca2+-independent protein kinase C.
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ABSTRACT: Bradykinin has long been known to excite sympathetic neurons via B(2) receptors, and this action is believed to be mediated by an inhibition of M-currents via phospholipase C and inositol trisphosphate-dependent increases in intracellular Ca(2+). In primary cultures of rat superior cervical ganglion neurons, bradykinin caused an accumulation of inositol trisphosphate, an inhibition of M-currents, and a stimulation of action potential-mediated transmitter release. Blockade of inositol trisphosphate-dependent signaling cascades failed to affect the bradykinin-induced release of noradrenaline, but prevented the peptide-induced inhibition of M-currents. In contrast, inhibition or downregulation of protein kinase C reduced the stimulation of transmitter release, but not the inhibition of M-currents, by bradykinin. In cultures of superior cervical ganglia, classical (alpha, betaI, betaII), novel (delta, epsilon), and atypical (zeta) protein kinase C isozymes were detected by immunoblotting. Bradykinin induced a translocation of Ca(2+)-independent protein kinase C isoforms (delta and epsilon) from the cytosol to the membrane of the neurons, but left the cellular distribution of other isoforms unchanged. This activation of Ca(2+)-independent protein kinase C enzymes was prevented by a phospholipase C inhibitor. The bradykinin-dependent stimulation of noradrenaline release was reduced by inhibitors of classical and novel protein kinase C isozymes, but not by an inhibitor selective for Ca(2+)-dependent isoforms. These results demonstrate that bradykinin B(2) receptors are linked to phospholipase C to simultaneously activate two signaling pathways: one mediates an inositol trisphosphate- and Ca(2+)-dependent inhibition of M-currents, the other one leads to an excitation of sympathetic neurons independently of changes in M-currents through an activation of Ca(2+)-insensitive protein kinase C.
SUBMITTER: Scholze T
PROVIDER: S-EPMC6757910 | biostudies-literature | 2002 Jul
REPOSITORIES: biostudies-literature
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