TY - JOUR T1 - Neomycin Inhibits Catecholamine Secretion by Blocking Nicotinic Acetylcholine Receptors in Bovine Adrenal Chromaffin Cells JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 73 LP - 80 VL - 288 IS - 1 AU - Kyong-Tai Kim AU - Se-Young Choi AU - Tae-Ju Park Y1 - 1999/01/01 UR - http://jpet.aspetjournals.org/content/288/1/73.abstract N2 - We investigated the effects of neomycin on nicotinic acetylcholine receptor-induced responses in bovine adrenal chromaffin cells. Neomycin inhibited the nicotinic agonist dimethylphenylpiperazinium iodide (DMPP)-induced norepinephrine secretion in a concentration-dependent manner. Neomycin had also an inhibitory effect on the DMPP-induced increase in cytosolic Ca++ concentration ([Ca++]i). This effect was further confirmed by inhibition of the DMPP-induced fluorescence quenching of fura-2 upon Mn++ entry. Under the same conditions, however, neomycin did not change the bradykinin-induced [Ca++]i increase, which follows the downstream signal of phospholipase C phospholipase C activation in this cell. The inhibitory effect of neomycin on the DMPP-induced [Ca++]i increase was apparent when the neomycin treatment was performed simultaneously with DMPP, suggesting a direct action on the nicotinic receptor. The direct inhibitory action of neomycin on the nicotinic receptor was also evident when neomycin inhibited the DMPP-induced cytosolic Ca++ increase, which is not affected by nifedipine nor ω-conotoxin MVIIC, and the cytosolic Na+ increase, which is not affected by tetrodotoxin. In addition, we observed that neomycin inhibited the binding of nicotine to the acetylcholine receptor in a noncompetitive manner. The data suggest that neomycin inhibits the nicotinic acetylcholine receptor directly, which results in blockage of the nicotinic receptor-mediated signaling without involvement of phospholipase C. The American Society for Pharmacology and Experimental Therapeutics ER -