Involvement of protein kinase C in the presynaptic nicotinic modulation of [³H]‐dopamine release from rat striatal synaptosomes

Abstract

1 Presynaptic nicotinic ACh receptors modulate transmitter release in the brain. Here we report their interactions with protein kinase C (PKC) with respect to [ 3 H]-dopamine release from rat striatal synaptosomes, monitored by superfusion. 2 Two speci®c PKC inhibitors, Ro 31-8220 (1 mM) and D-erythro-sphingosine (10 mM) signi®cantly reduced (by 51 and 26% respectively) [ 3 H]-dopamine release stimulated by anatoxin-a (AnTx), a potent and selective agonist of nicotinic ACh receptors. The inactive structural analogue of Ro 31-8220, bisindolylmaleimide V (1 mM) had no e ect. 3 Two phorbol esters, PDBu (1 mM) and PMA (1 mM) potentiated AnTx-evoked [ 3 H]-dopamine release by 50 ± 80%. This was Ca 2+ -dependent and prevented by PKC inhibitors. In the absence of nicotinic agonist, phorbol esters enhanced basal release through a PKC-independent mechanism. 4 A 86 Rb + e ux assay of nicotinic ACh receptor function con®rmed that Ro 31-8220 has no nonspeci®c e ect on presynaptic nicotinic ACh receptors. 5 These results suggest that PKC is activated by nicotinic ACh receptor stimulation and mediates a component of AnTx-evoked [ 3 H]-dopamine release. In addition, independent activation of PKC can further amplify the response, o ering a potential mechanism for receptor crosstalk.

Nicotinic acetylcholine receptor-mediated calcium signaling in the nervous system

“…For example, protein kinase C (PKC) has been proposed to modulate striatal dopamine release by nAChR activation [44] . Furthermore, nAChR and PKC-mediated stimulation of extracellular signal-regulated mitogen-activated protein kinase (ERK/MAPK) [45] and annexin phosphorylation [46] have been reported to contribute to the regulation of exocytosis in adrenomedullary cells.…”

Presynaptic BK type Ca2+-activated K+ channels are involved in prostanoid TP receptor-mediated inhibition of noradrenaline release from the rat gastric sympathetic nerves

“…Diacylglycerol functions as an intracellular second messenger to activate PKC (Nishizuka, 1992 (Soliakov and Wonnacott, 2001) and the phorbol ester-induced activation of PKC in the rat calyx of Held synapse at 3 μM (Korogod et al, 2007;Lou et al, 2008). In the present experiment, Ro 31-8220 even at 3 μM had no effect on the prostanoid TP receptor-mediated response, suggesting that the neuronal PKC is not involved in the prostanoid TP receptor-mediated inhibition of gastric noradrenaline release in rats.…”

Translational Research in Nicotine Dependence

“…These receptors are pentameric ion channels, which pass Na þ , K þ , and Ca 2þ ions and thus have the ability to alter cellular activity. Entry of these ions can either directly impact cell excitability or trigger calcium-sensitive molecules, such as protein kinase C (PKC) (Soliakov and Wonnacott 2001), protein kinase A (PKA) (Dajas-Bailador et al 2002), calmodulin-dependent protein kinase II (CAMKII) (Steiner et al 2007), and extracellular signal-regulated kinases (ERKs) (Dajas-Bailador et al 2002;Steiner et al 2007). These calcium-sensitive kinases then have myriad downstream effects, including activation of transcription factors such as CREB (Chang and Berg 2001;Pandey et al 2001;Hu et al 2002;Brunzell et al 2003;Walters et al 2005) (for a review of signaling effects of nicotine, see Shen and Yakel 2009).…”