L. Soliakov et S. Wonnacott, Involvement of protein kinase C in the presynaptic nicotinic modulation of[H-3]-dopamine release from rat striatal synaptosomes, BR J PHARM, 132(3), 2001, pp. 785-791
1 Presynaptic nicotinic ACh receptors modulate transmitter release in the b
rain. Here we report their interactions with protein kinase C (PKC) with re
spect to [H-3]-dopamine release from rat striatal synaptosomes, monitored b
y superfusion.
2 Two specific PKC inhibitors, Ro 31-8220 (1 muM) and D-erythro-sphingosine
(10 muM) significantly reduced (by 51 and 26% respectively) [H-3]-dopamine
release stimulated by anatoxin-a (AnTx), a potent and selective agonist of
nicotinic ACh receptors. The inactive structural analogue of Ro 31-8220, b
isindolylmaleimide V (1 muM) had no effect.
3 Two phorbol esters, PDBu (1 muM) and PMA (1 muM) potentiated AnTx-evoked
[H-3]-dopamine release by 50-80%. This was Ca2+-dependent and prevented by
PKC inhibitors. In the absence of nicotinic agonist, phorbol esters enhance
d basal release through a PKC-independent mechanism.
4 A Rb-86(+) efflux assay of nicotinic ACh receptor function confirmed that
Ro 31-8220 has no nonspecific effect on presynaptic nicotinic ACh receptor
s.
5 These results suggest that PKC is activated by nicotinic ACh receptor sti
mulation and mediates a component of AnTx-evoked [H-3]-dopamine release. In
addition, independent activation of PKC can further amplify the response,
offering a potential mechanism for receptor crosstalk.