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Otilonium bromide inhibits calcium entry through L‐type calcium channels in human intestinal smooth muscle
Author(s) -
Strege P. R.,
Evangelista S.,
Lyford G. L.,
Sarr M. G.,
Farrugia G.
Publication year - 2004
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/j.1365-2982.2004.00517.x
Subject(s) - patch clamp , endocrinology , chemistry , calcium , medicine , intracellular , voltage dependent calcium channel , l type calcium channel , microbiology and biotechnology , biophysics , electrophysiology , biology , biochemistry
Otilonium bromide (OB) is used as an intestinal antispasmodic. The mechanism of action of OB is not completely understood. As Ca 2+ entry into intestinal smooth muscle is required to trigger contractile activity, our hypothesis was that OB blocked Ca 2+ entry through L‐type Ca 2+ channels. Our aim was to determine the effects of OB on Ca 2+ , Na + and K + ion channels in human jejunal circular smooth muscle cells and on L‐type Ca 2+ channels expressed heterologously in HEK293 cells. Whole cell currents were recorded using standard patch clamp techniques. Otilonium bromide (0.09–9 μ mol L −1 ) was used as this reproduced clinical intracellular concentrations. In human circular smooth muscle cells, OB inhibited L‐type Ca 2+ current by 25% at 0.9 μ mol L −1 and 90% at 9 μ mol L −1 . Otilonium bromide had no effect on Na + or K + currents. In HEK293 cells, 1 μ mol L −1 OB significantly inhibited the expressed L‐type Ca 2+ channels. Truncation of the α 1C subunit C and N termini did not block the inhibitory effects of OB. Otilonium bromide inhibited Ca 2+ entry through L‐type Ca 2+ at concentrations similar to intestinal tissue levels. This effect may underlie the observed muscle relaxant effects of the drug.