The effects of anandamide transport inhibitor AM404 on voltage-dependent calcium channels

Alp Alptekin, Sehammuddin Galadari, Yaroslav Shuba, Georg Petroianu, Murat Oz

Research output: Contribution to journalArticlepeer-review

Abstract

The effects of anandamide transport inhibitor AM404 were investigated on depolarization-induced 45Ca2+ fluxes in transverse tubule membrane vesicles from rabbit skeletal muscle and on Ba2+ currents through L-type voltage-dependent Ca2+ channels in rat myotubes. AM404, at the concentration of 3μM and higher, caused a significant inhibition of 45Ca2+ fluxes. Radioligand binding studies indicated that the specific binding of [3H]Isradipine to transverse tubule membranes was also inhibited significantly by AM404. In controls and in presence of 10μM AM404, Bmax values were 51±6 and 27±5pM/mg, and KD values were 236±43 and 220±37pM, respectively. Inhibitory effects of AEA and arachidonic acid on 45Ca2+ flux and [3H]Isradipine binding reported in earlier studies, were also enhanced significantly in the presence of AM404. In the presence of VDM11 (1μM), another anandamide transport inhibitor, AM404 continued to inhibit 45Ca2+ fluxes and [3H]Isradipine binding. In rat myotubes, Ca2+ currents through L-type Ca2+ channels recorded in whole-cell configuration of patch clamp technique were inhibited by AM404 in a concentration-dependent manner with an IC50 value of 3.2μM. In conclusion, results indicate that AM404 inhibits directly the function of L-type voltage-dependent Ca2+ channels in mammalian skeletal muscles.

Original languageEnglish (US)
Pages (from-to)10-15
Number of pages6
JournalEuropean Journal of Pharmacology
Volume634
Issue number1-3
DOIs
StatePublished - May 2010

Keywords

  • AM404
  • Calcium channel
  • Endocannabinoid
  • Skeletal muscle

ASJC Scopus subject areas

  • Pharmacology

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