The effects of a diacylglycerol kinase inhibitor at mammalian and amphibian neuromuscular junctions in vitro

Miniature endplate potentials were studied in mouse phrenic nerve-hemidiaphragm and frog pectoris-cutaneous neuromuscular preparations. The diacylglycerol kinase inhibitor R59022 increased the frequency of miniature endplate potentials in both preparations. The results indicate that endogenous diacylglycerol regulates acetylcholine release via activation of protein kinase C. Continuous monitoring of miniature endplate potential frequency in the frog preparation showed that higher doses of the inhibitor caused a large rise in release rate, which subsequently settled at a lower, though still augmented, level. It is suggested that a negative feedback may occur in response to high protein kinase C activity, possibly to inhibit diacylglycerol generation.