In:
The Journal of Neuroscience, Society for Neuroscience, Vol. 22, No. 14 ( 2002-07-15), p. 5823-5832
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 (α, βI, βII), novel (δ, ε), and atypical (ζ) protein kinase C isozymes were detected by immunoblotting. Bradykinin induced a translocation of Ca 2+ -independent protein kinase C isoforms (δ and ε) 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.
Type of Medium:
Online Resource
ISSN:
0270-6474
,
1529-2401
DOI:
10.1523/JNEUROSCI.22-14-05823.2002
Language:
English
Publisher:
Society for Neuroscience
Publication Date:
2002
detail.hit.zdb_id:
1475274-8
SSG:
12
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