Modulation of acetylcholine release from mouse cortex by protein kinase C: dependence on stimulation intensity.
Activation of protein kinase C (PKC) results in enhanced action-potential evoked release of a variety of transmitters. However, previous studies have suggested that acetylcholine release is poorly modulated by PKC compared to other transmitter types. We investigated the effect of stimulation conditions on PKC modulation of electrical stimulation-induced acetylcholine release in mouse cortex, which were incubated with [3H]choline. The PKC activator phorbol dibutyrate (PDB) enhanced acetylcholine release at low stimulation frequencies (0.1 and 0.5 Hz) and not at 3 or 10 Hz. At 3 Hz stimulation, when release was inhibited by neostigmine, PDB enhanced acetylcholine release, suggesting that at low levels of acetylcholine release, exogenous activation of PKC can elevate acetylcholine release. However, at higher frequencies, PKC may already be endogenously activated since the PKC inhibitor polymyxin B (PXB) inhibited acetylcholine release. The other PKC inhibitors, Ro 318220, Gö 6976, bisindolylmaleimide and calphostin C appeared to have no effect at 3 Hz. It may be that these inhibitors do not effectively block PKC in this functional system. Indeed, polymyxin B completely blocked the facilitatory effect of PDB but Ro 318220 was without effect.
Iannazzo
L
L
Prince Henry's Institute of Medical Research, Clayton, Victoria, Australia. lydia.iannazzo@RMIT.edu.au
Kotsonis
P
P
Majewski
H
H
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D051379:Mice; D009388:Neostigmine / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011112:Polymyxin B / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*
D004791:Enzyme Inhibitors; D015240:Phorbol 12,13-Dibutyrate; D009388:Neostigmine; D011493:Protein Kinase C; D011112:Polymyxin B; D000109:Acetylcholine