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Title
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Inhibition of -sensitive currents in NG 108-15 cells by substance P and related tachykinins
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Author
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Abstract
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| 1 The whole-cell patch-clamp technique was used to investigate the actions of substance P and other agonists at neurokinin (NK) receptors on voltage-gated K+ and Ca+ channel currents in undifferentiated mouse neuroblastoma x rat glioma NG 108-15 cells. 2 Both substance P (0.3-30 mu M) and the NK1 receptor selective agonist GR73632 (10 nM-10 mu M) caused concentration-dependent inhibition of K+ currents. GR64349 and senktide (agonists at NK2 and NK3 receptors respectively) also inhibited K+ currents, but only at concentrations which were several orders of magnitude greater than GR73632, suggesting that current inhibition was mediated via NK1 receptors. 3 Substance P and GR73632 were without effect on residual K+ currents recorded in the presence of extracellular Co2+ (4 mM) to abolish the Ca2+-sensitive component (IKCa) of the K+ current. Ca2+ channel currents, recorded with either Ba2+ or Ca2+ as charge carrier, were unaffected by NK1, NK2 and NK3 receptor ligands. 4 Iontophoretic application of GR73632 produced a current-dependent reduction of K+ currents. In the presence of the non-peptide NK1 antagonists, CP-99,994 and RP67580, and the peptide antagonist, GR82334, the current-response relationship was reversibly shifted to the right. This indicates that the response is mediated by NK1 receptors. 5 Our results indicate that activation of NK1 receptors leads to the selective inhibition of IKCa in undifferentiated NG 108-15 cells. |
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Language
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English
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Source (journal)
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British journal of pharmacology. - London
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Publication
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London
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1996
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ISSN
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0007-1188
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DOI
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10.1111/J.1476-5381.1996.TB15988.X
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Volume/pages
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119
:2
(1996)
, p. 315-320
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ISI
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A1996VG29800022
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Full text (Publisher's DOI)
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