Pflügers Archiv

, Volume 424, Issue 5–6, pp 516–522 | Cite as

Bell-shaped activation of inositol-1,4,5-trisphosphate-induced Ca2+ release by thimerosal in permeabilized A7r5 smooth-muscle cells

  • Jan B. Parys
  • Ludwig Missiaen
  • Humbert De Smedt
  • Guy Droogmans
  • Rik Casteels
Heart, Circulation, Respiration and Blood; Environmental and Exercise Physiology
Received:
Revised:
Accepted:

Abstract

There is no consensus about the different types of Ca2+ transport processes in the endoplasmic reticulum that are targeted by the sulphydryl reagent thimerosal. We have therefore investigated how thimerosal affects the various Ca2+ transport processes in permeabilized A7r5 smooth-muscle cells, using an unidirectional 45Ca2+ flux technique. Thimerosal up to a concentration of 32 μM did not have an effect on the passive 45Ca2+ leak from the stores, while higher concentrations increased this aspecific leak. Thimerosal inhibited the endoplasmic reticulum Ca2+ pump with an EC50 of 9 μM. Thimerosal exerted a biphasic effect on the Ca2+ release induced by inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] with a stimulation of the release at thimerosal concentrations below 10 μM, and an inhibitory effect at higher concentrations. Thimerosal (2.5–250 μM) did not exert an effect on the specific binding of [3H]Ins(1,4,5)P3 to its receptor, indicating that it probably did not act at the level of the binding site. This finding contrasts with the effect of the closely related sulphydryl reagent parachloromercuriphenylsulphonate, which, at high concentrations, inhibited [3H]Ins(1,4,5)P3 binding. The effects of thimerosal were largely prevented by the sulphydryl reducing agent dithiothreitol (3 mM). We conclude that thimerosal concentrations ranging from 0.32 to 1 μM can stimulate the Ins(1,4,5)P3-induced Ca2+ release without inhibiting the Ca2+ pumps or without increasing the passive Ca2+ permeability of the endoplasmic reticulum.

Key words

Thimerosal Ins(1,4,5)P3 receptor Ca2+ signalling 
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Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • Jan B. Parys
    • 1
  • Ludwig Missiaen
    • 1
  • Humbert De Smedt
    • 1
  • Guy Droogmans
    • 1
  • Rik Casteels
    • 1
  1. 1.Laboratorium voor FysiologieK. U. LeuvenLeuvenBelgium

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