Abstract
Otilonium bromide (OB) is used as an intestinal antispasmodic. The mechanism of action of OB is not completely understood. As Ca2+ entry into intestinal smooth muscle is required to trigger contractile activity, our hypothesis was that OB blocked Ca2+ 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 Ca2+ channels expressed heterologously in HEK293 cells. Whole cell currents were recorded using standard patch clamp techniques. Otilonium bromide (0.09-9 μmol L-1) was used as this reproduced clinical intracellular concentrations. In human circular smooth muscle cells, OB inhibited L-type Ca2+ current by 25% at 0.9 μmol L-1 and 90% at 9 μmol L-1. Otilonium bromide had no effect on Na+ or K+ currents. In HEK293 cells, 1 μmol L-1 OB significantly inhibited the expressed L-type Ca 2+ channels. Truncation of the α1C subunit C and N termini did not block the inhibitory effects of OB. Otilonium bromide inhibited Ca2+ entry through L-type Ca2+ at concentrations similar to intestinal tissue levels. This effect may underlie the observed muscle relaxant effects of the drug.
Original language | English (US) |
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Pages (from-to) | 167-173 |
Number of pages | 7 |
Journal | Neurogastroenterology and Motility |
Volume | 16 |
Issue number | 2 |
DOIs | |
State | Published - Apr 2004 |
Keywords
- Calcium
- Ion channels
- Irritable bowel syndrome
- Otilonium bromide
- Patch clamp
- Small intestine
ASJC Scopus subject areas
- Physiology
- Endocrine and Autonomic Systems
- Gastroenterology