RT Journal Article
SR Electronic
T1 Second messengers involved in the mechanism of action of bradykinin in sensory neurons in culture
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 3314
OP 3325
DO 10.1523/JNEUROSCI.09-09-03314.1989
VO 9
IS 9
A1 GM Burgess
A1 I Mullaney
A1 M McNeill
A1 PM Dunn
A1 HP Rang
YR 1989
UL http://www.jneurosci.org/content/9/9/3314.abstract
AB Application of bradykinin to neonatal rat dorsal root ganglion neurons caused a depolarization associated with an inward current and an increase in membrane conductance that was probably due to the opening of sodium channels. No hyperpolarization or outward current was detected. In addition, bradykinin increased the rate of 45Ca uptake into the neurons by a mechanism that was blocked by the dihydropyridine calcium channel antagonist nifedipine. Direct activation of protein kinase C (PKC) with phorbol esters mimicked the ability of bradykinin to depolarize the neurons and to increase the rate of 45Ca uptake. Down- regulation of PKC by prolonged treatment with phorbol esters and treatment of the cells with staurosporine, which inhibits PKC, blocked both bradykinin- and phorbol ester-induced 45Ca influx, and substantially reduced the proportion of cells that gave electrophysiological responses to either agent. Bradykinin also activated polyphosphoinositidase C in the dorsal root ganglion neurons, elevating levels of inositol(1,4,5)-trisphosphate and 1,2- diacylglycerol, an endogenous activator of PKC. It is suggested, therefore, that PKC may mediate some of the effects of bradykinin in sensory neurons.