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Research ArticleArticle

Neomycin Inhibits Catecholamine Secretion by Blocking Nicotinic Acetylcholine Receptors in Bovine Adrenal Chromaffin Cells

Kyong-Tai Kim, Se-Young Choi and Tae-Ju Park
Journal of Pharmacology and Experimental Therapeutics January 1999, 288 (1) 73-80;
Kyong-Tai Kim
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Se-Young Choi
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Tae-Ju Park
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Abstract

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.

Footnotes

  • Send reprint requests to: Kyong-Tai Kim, Doctor of Philosophy, Department of Life Science, POSTECH, San 31, Hyoja Dong, Pohang, 790-784, Republic of Korea.

  • 1 This work was supported by grants from the Hallym Academy of Sciences, Hallym University, the Korea Science, and Engineering Foundation (KOSEF 95-0401-02), and the Basic Science Research Institute Program (Project BSRI-96-4435) of the Ministry of Education.

  • Abbreviations:
    DMPP
    dimethylphenylpiperazinium iodide
    InsP3
    inositol 1,4,5-trisphosphate
    [Ca++]i
    cytosolic calcium ion concentration
    [Na+]i
    cytosolic sodium ion concentration
    IC50
    half-maximal inhibitory concentration
    SBFI/AM
    sodium binding furan isophthalate tetraacetoxymethyl ester
    PLC
    phospholipase C
    PIP2
    phosphatidyl inositol 4,5-bisphosphate
    • Received February 4, 1998.
    • Accepted July 14, 1998.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 288 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 288, Issue 1
1 Jan 1999
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Research ArticleArticle

Neomycin Inhibits Catecholamine Secretion by Blocking Nicotinic Acetylcholine Receptors in Bovine Adrenal Chromaffin Cells

Kyong-Tai Kim, Se-Young Choi and Tae-Ju Park
Journal of Pharmacology and Experimental Therapeutics January 1, 1999, 288 (1) 73-80;

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Research ArticleArticle

Neomycin Inhibits Catecholamine Secretion by Blocking Nicotinic Acetylcholine Receptors in Bovine Adrenal Chromaffin Cells

Kyong-Tai Kim, Se-Young Choi and Tae-Ju Park
Journal of Pharmacology and Experimental Therapeutics January 1, 1999, 288 (1) 73-80;
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