Otilonium bromide inhibits calcium entry through L-type calcium channels in human intestinal smooth muscle

P. R. Strege, S. Evangelista, G. L. Lyford, M. G. Sarr, G. Farrugia

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

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 languageEnglish (US)
Pages (from-to)167-173
Number of pages7
JournalNeurogastroenterology and Motility
Volume16
Issue number2
DOIs
StatePublished - 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

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