PMID- 10428009
OWN - NLM
STAT- MEDLINE
DCOM- 19990910
LR  - 20190826
IS  - 0306-3623 (Print)
IS  - 0306-3623 (Linking)
VI  - 33
IP  - 1
DP  - 1999 Jul
TI  - Thimerosal: a versatile sulfhydryl reagent, calcium mobilizer, and cell 
      function-modulating agent.
PG  - 1-6
AB  - An overview of the literature concerning the effects of thimerosal is presented. 
      Because of its antibacterial effect, thimerosal is used for a variety of 
      practical purposes such as antiseptic and preservative. In biomedical studies, 
      thimerosal is used as a sulfhydryl reagent, and as a calcium-mobilizing agent. 
      The ability of thimerosal to act as a sulfhydryl group is related to the presence 
      of mercury. Relatively little study has been devoted to the mechanism of the 
      reaction of thimerosal with the sulfhydryl group; the sulfhydryl reactive 
      capacity is mostly concluded on the basis of inactivation of the effect by 
      dithiothreitol (DTT). Thimersal causes a release of calcium from intracellular 
      stores in many cells types; this is followed by an influx of extracellular 
      calcium. Both InsP3- and ryanodine-sensitive calcium stores may be affected. 
      Studies with permeabilized cells or organelles show that the effect of thimerosal 
      on calcium is dependent on the concentration: low concentrations of thimerosal 
      stimulate calcium release, high concentrations are inhibitory. This dependence is 
      not found in intact cells. Thimerosal may activate or inhibit a number of cell 
      functions. These are often related to the ability to release calcium or with the 
      sulfhydryl reactivity. In platelets, thimerosal causes aggregation, increase of 
      arachidonic acid metabolism, and exocytotic release of serotonin. In neutrophils, 
      thimerosal causes, besides an increase of cytosolic free calcium, an increase of 
      formyl-methionyl-leucyl-phenylalanine (fMLP)-activated leukotriene release, and a 
      modulation of chemotactic migration and exocytosis. At low concentrations, 
      thimerosal induces chemotactic migration of neutrophils, in the absence of other 
      chemoattractants. The effect is also observed with thiosalicylic acid, indicating 
      that the stimulation of migration was due to the thiosalicylic acid moiety of the 
      thimerosal molecule. At higher concentrations, thimerosal causes inhibition of 
      fMLP-activated migration. Low concentrations of thimerosal, but not of 
      thiosalicylic acid, induced exocytotic enzyme release from neutrophils. High 
      concentrations of thimerosal inhibited fMLP-activated exocytosis. The results 
      point to an involvement of calcium mobilization and calcium influx of activation, 
      and reaction with sulfhydryl groups for inhibition.
FAU - Elferink, J G
AU  - Elferink JG
AD  - Department of Molecular Cell Biology, University of Leiden, The Netherlands.
LA  - eng
PT  - Journal Article
PT  - Review
PL  - England
TA  - Gen Pharmacol
JT  - General pharmacology
JID - 7602417
RN  - 0 (Anti-Infective Agents, Local)
RN  - 0 (Sulfhydryl Reagents)
RN  - 2225PI3MOV (Thimerosal)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Anti-Infective Agents, Local/*pharmacology
MH  - Calcium/metabolism
MH  - Cell Physiological Phenomena/drug effects
MH  - Humans
MH  - Sulfhydryl Reagents/pharmacology
MH  - Thimerosal/*pharmacology
RF  - 32
EDAT- 1999/07/31 00:00
MHDA- 1999/07/31 00:01
CRDT- 1999/07/31 00:00
PHST- 1999/07/31 00:00 [pubmed]
PHST- 1999/07/31 00:01 [medline]
PHST- 1999/07/31 00:00 [entrez]
AID - S0306362398002584 [pii]
AID - 10.1016/s0306-3623(98)00258-4 [doi]
PST - ppublish
SO  - Gen Pharmacol. 1999 Jul;33(1):1-6. doi: 10.1016/s0306-3623(98)00258-4.