[Neomycin inhibits nicotinic receptor-mediated response in pheochromocytoma (PC12) cells]

Neomycin is one of the aminoglycoside antibiotics, and on the cellular level it inhibits phospholipase C. The effects of neomycin on the acetylcholine (ACh)-induced current (I(ACh)) were studied in pheochromocytoma (PC12) cells by using the whole-cell clamp technique. The I(ACh) on PC12 cells proved to be generated through activation of the neuronal nicotinic receptor. ACh (30 micromol/L) induced an inward current at a holding potential of -80 mV. When the cells were applied with neomycin (0.01~1 mmol/L) and ACh (30 micromol/L) simultaneously, an inhibitory effect of neomycin on the peak of I(ACh) was observed. This effect was fast, reversible and concentration-dependent. Pretreatment with neomycin for 3~8 min had no influence on its inhibitory effect. Activation of protein kinase C by using an exogenous activator exerted an inhibitory action on I(ACh). However, intracellular dialysis with a PKC inhibitor (PKCI 19-31, 0.1~5 micromol/L) did not affect the inhibitory effect of neomycin. The results obtained suggest that neomycin exerts an inhibitory effect on I(ACh) without involvement of the blockage of phospholipase C.