Actions of 8-(N,N-diethylamino)-n-octyl-3,4,5-trimethoxybenzoate in vascular smooth muscle cell cultures

AIM: To study the effects of
8-(N,N-diethylamino)-n-octyl-3,4,5-trimethoxybenzoate (TMB-8) on vascular smooth
muscle (VSM) cells A7r5.
METHODS: The effects of TMB-8 were investigated in A7r5 cell cultures with
45CaCl2.
RESULTS: TMB-8 reduced the intracellular free Ca2+ concentration, [Ca2+]i in a
Ca(2+)-free medium and blocked Ca2+ entry from the extracellular site in a
regular Ca2+ medium. The equilibrated total cellular binding of Ca2+ was
increased by TMB-8 whereas 45Ca2+ entry activated by both NE and KCl was
inhibited. However, the NE-activated Ca2+ entry was not blocked by TMB-8 if TMB-8
was added together with 45Ca2+ at a later time instead of by pretreatment.
Similar to actions of NE and KCl, depletion of Ca2+ from sarcoplasmic reticulum
(SR) would also activate Ca2+ entry, which was blocked by TMB-8. When TMB-8 was
rinsed out alone or together with NE after pretreatment with NE plus TMB-8 in VSM
cells, the inhibitory effect of TMB-8 was not affected.
CONCLUSION: TMB-8 not only blocks Ca2+ entry from the extracellular site, but
also enhances Ca2+ uptake into SR which, indirectly inhibits Ca2+ entry from the
extracellular site.