Neomycin inhibits catecholamine secretion by blocking nicotinic acetylcholine receptors in bovine adrenal chromaffin cells.
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 omega-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.
Kim
K T
KT
Department of Life Science, Pohang University of Science and Technology, Pohang, Republic of Korea.
Choi
S Y
SY
Park
T J
TJ
D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D019439:Chromaffin Cells / Q000187:drug effects* / Q000378:metabolism; D005089:Exocytosis / Q000187:drug effects; D008012:Lidocaine / Q000494:pharmacology; D009355:Neomycin / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects
D000900:Anti-Bacterial Agents; D002395:Catecholamines; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D008012:Lidocaine; D009355:Neomycin; D002118:Calcium; D009638:Norepinephrine