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PubMed1991

A probable role for vaccines containing thimerosal in thimerosal hypersensitivity.

We patch tested 141 patients with 0.05% aq. thimerosal and 222 patients with 0.05% aq. mercuric chloride, including 63 children. The frequency of positive patch test reactions to thimerosal was 16.3%. There was a marked preponderance in the young age groups after vaccination, while none of 36 infants (aged 3-48 months) reacted to thimerosal. Positive reactions to mercuric chloride were found in 23 (10.4%) of 222 patients. We also sensitized guinea pigs with diphtheria-pertussis-tetanus (DPT) vaccine containing 0.01% thimerosal and succeeded in inducing hypersensitivity to thimerosal. From patch testing in humans and animal experiments, it is suggested that 0.01% thimerosal in vaccines can sensitize children, and that hypersensitivity to thimerosal is due to the thiosalicylic part of the molecule and correlates with photosensitivity to piroxicam.

Adolescent↗

PubMed1992

The thiol reagent, thimerosal, evokes Ca2+ spikes in HeLa cells by sensitizing the inositol 1,4,5-trisphosphate receptor.

The thiol reagent, thimerosal, has been shown to cause an increase in intracellular Ca2+ concentration ([Ca2+]i) in several cell types, and to cause Ca2+ spikes in unfertilized hamster eggs. Using single cell video-imaging we have shown that thimerosal evokes repetitive Ca2+ spikes in intact Fura-2-loaded HeLa cells that were similar in shape to those stimulated by histamine. Both thimerosal- and histamine-stimulated Ca2+ spikes occurred in the absence of extracellular (Ca2+ o), suggesting that they result from mobilization of Ca2+ from intracellular stores. Whereas histamine stimulated formation of inositol phosphates, thimerosal, at concentrations that caused sustained Ca2+ spiking, inhibited basal and histamine-stimulated formation of inositol phosphates. Thimerosal-evoked Ca2+ spikes are therefore not due to the stimulated production of inositol 1,4,5-trisphosphate (InsP3). The effects of thimerosal on Ca2+ spiking were probably due to alkylation of thiol groups on intracellular proteins because the spiking was reversed by the thiol-reducing compound dithiothreitol, and the latency between addition of thimerosal and a rise in [Ca2+]i was greatly shortened in cells where the intracellular reduced glutathione concentration had been decreased by preincubation with DL-buthionine (S,R)-sulfoximine. In permeabilized cells, thimerosal caused a concentration-dependent inhibition of Ca2+ accumulation, which was entirely due to inhibition of Ca2+ uptake into stores because thimerosal did not affect unidirectional 45Ca2+ efflux from stores preloaded with 45Ca2+. Thimerosal also caused a concentration-dependent sensitization of InsP3-induced Ca2+ mobilization: half-maximal mobilization of Ca2+ stores occurred with 161 +/- 20 nM InsP3 in control cells and with 62 +/- 5 nM InsP3 after treatment with 10 microM thimerosal. We conclude that thimerosal can mimic the effects of histamine on intracellular Ca2+ spiking without stimulating the formation of InsP3 and, in light of our results with permeabilized cells, suggest that thimerosal stimulates spiking by sensitizing cells to basal InsP3 levels.

Calcium↗

PubMed1992

Cytosolic Ca2+ spikes evoked by the thiol reagent thimerosal in both intact and internally perfused single pancreatic acinar cells.

Cytosolic calcium signals evoked by the sulphydryl-group-oxidising agent, thimerosal, have been investigated in acutely isolated pancreatic acinar cells. Two techniques were employed for the assessment of the cytosolic free-calcium concentration ([Ca2+]i): measurement of calcium-dependent chloride and non-specific cation currents (whole-cell patch-clamp recording) and microfluorimetry (fura-2). Thimerosal (0.5-100 microM) evoked repetitive spikes in both chloride and cation currents as seen by patch-clamp recording, and in [Ca2+]i as seen by microfluorimetry, with a latency of 1-3 min. The response increased in magnitude over time and was not reversed on removal of thimerosal. The thimerosal-induced spikes were reversibly blocked by 2 mM dithiothreitol and by 20 mM caffeine. Inclusion of heparin (200 micrograms/ml) in the pipette solution blocked the thimerosal-induced spikes. The calcium spikes continued after the removal of extracellular calcium; however, low concentrations of thimerosal (0.5-5 microM) were unable to initiate a current response in the absence of external calcium. High concentrations of thimerosal (50-100 microM) could initiate spikes without extracellular calcium. Thimerosal, at concentrations that failed to produce an independent effect, potentiated the acetylcholine-evoked oscillations in [Ca2+]i. We conclude that thimerosal is able to mobilise calcium from an intracellular store; the blockade by heparin may indicate that thimerosal exerts an action on the inositol trisphosphate pathway. The dependence on extracellular calcium for initiation, but not for continuation of the thimerosal-induced calcium spikes suggests that thimerosal may have the additional effect of inhibiting the plasma membrane calcium ATPase.

Action Potentials↗

PubMed1988

Thimerosal: an ophthalmic preservative which acts as a hapten to elicit specific antibodies and cell mediated immunity.

A rabbit model for the study of hypersensitivity to thimerosal was established in order to develop better techniques for screening patient sera and tears for specific antibodies to lens care re-agents. Thimerosal (sodium ethylmercury thiosalicylatelate) was successfully coupled to several protein carriers using a water soluble carbodiimide which linked the carboxyl group of thimerosal to free amino groups of the carrier proteins. Thimerosal was also shown to spontaneously react with proteins as detected by the irreversible binding of mercury to the protein carrier. Immunization of rabbits with the chemically coupled thimerosal resulted in the production of antibodies which specifically reacted with thimerosal. The rabbits also manifested delayed and immediate forms of hypersensitivity to the thimerosal conjugates. The ELISA assay for specific serum antibodies was found to be a sensitive, reliable and specific screening tool However, there was no immunological cross reactivity between the chemically coupled thimerosal and the spontaneously coupled thimerosal. Therefore, the epitopes produced by these two reaction mechanisms were probably immunochemically different even though both contained detectable thimerosal derived mercury.

Animals↗

PubMed1992

Effect of the sulfhydryl reagent thimerosal on cytosolic free Ca2+ and membrane potential of thymocytes.

The sulfhydryl reagent thimerosal at concentrations 5-100 microM has been found to induce a variety of changes in ion transport in rat thymocytes. In particular, [Ca2+]i increases about 10-fold from the basal level. The [Ca2+]i response to thimerosal displays a two-stage time course, with the main [Ca2+]i rise during the second stage. Evidence has been obtained for the depletion of intracellular Ca2+ pools in thimerosal-treated cells, however, Ca2+ mobilization from intracellular stores does not contribute significantly into [Ca2+]i rise. Thimerosal elicits permeability not only for Ca2+, but also for Mn2+ and Ni2+, which is Ca(2+)-dependent. We failed to get any evidence on thimerosal-induced inhibition of the plasma membrane Ca(2+)-ATPase. The induction of Ca2+ influx, rather than inhibition of Ca(2+)-ATPase, accounts for the disturbance of [Ca2+]i homeostasis in thimerosal-treated cells. Thimerosal also elicits changes in monovalent ion fluxes resulting in marked depolarization. The latter seems unrelated to the changes in [Ca2+]i and is suggested to be mediated both by increased permeability for Na+ and a decreased one for K+. Thimerosal significantly stimulates AA release from thymocytes. Evidence has been presented that AA metabolite(s), probably, LO product(s), may mediate the changes in the transport of mono- and divalent cations elicited by the sulfhydryl reagent. Prolonged treatment of thymocytes with thimerosal resulted in cell death.

Animals↗

PubMed1991

Thimerosal induces calcium mobilization, fructose 2,6-bisphosphate synthesis and cytoplasmic alkalinization in rat thymus lymphocytes.

The effect of thimerosal on intracellular calcium ([Ca2+]i), pH (pHi) and fructose 2,6-bisphosphate (Fru 2,6-P2) in thymus lymphocytes was investigated. The effect of thimerosal on cell growth was also examined. Thimerosal produced a dose-dependent increase in [Ca2+]i, pHi and in the level of fructose 2,6-bisphosphate. Thimerosal was, however, unable to produce cell proliferation and inhibited [3H]thymidine incorporation when cells were challenged with PHA and costimulator. In the absence of external calcium, thimerosal produced only a slight increase in [Ca2+]i. In Na(+)-containing buffer, thimerosal induced an initial acidification (0.05 +/- 0.01 pH units), followed by an alkalinization of 0.08 pH units/min, whereas in Na(+)-free media, pHi decreased 0.2 +/- 0.02 units and this acidification was maintained for more than 40 min. When external calcium was removed the initial acidification was unchanged and no further increase in pHi was observed. Polymyxin B, an inhibitor of protein kinase C, did not modify the initial thimerosal-induced acidification although pH returned to basal levels after 10 min. It was concluded that alkalinization induced by thimerosal is probably due to activation of the Na+/H+ exchanger and that changes in internal Ca2+, pH and metabolic rate are not sufficient to induce cellular proliferation. The mechanism by which thimerosal inhibits thymocyte proliferation remains to be clarified.

Animals↗

PubMed1992

Thimerosal blocks stimulated but not basal release of endothelium-derived relaxing factor (EDRF) in dog isolated coronary artery.

1. The effect of an acetly-coA lysolecithin acyltransferase inhibitor, thimerosal, on the release of endothelium-derived relaxing factor (EDRF) was examined in the greyhound isolated coronary artery. 2. Thimerosal (1-10 microM) relaxed fully, ring segments of coronary artery which were contracted with the thromboxane A2-mimetic, U46619 (30 nM). The response was endothelium-dependent, slow in both onset and time to reach maximum. The maximum relaxation to the highest concentration of thimerosal (10 microM) was maintained for 10-20 min before the tissue slowly regained active force (1-2 h) to the same or higher level as that prior to the addition of thimerosal. At this time the endothelium-dependent relaxation responses to acetylcholine (ACh), substance P (SP), bradykinin (BK) and the calcium ionophores, ionomycin and A23187 were abolished. The endothelium-dependent contractions to the nitric oxide synthase inhibitors, NG-nitro-L-arginine (L-NNA; 10-100 microM) and NG-monomethyl-L-arginine (L-NMMA: 10-100 microM), however, were unaffected. 3. Thimerosal (10 microM) did not affect the relaxation curve to sodium nitroprusside (SNP) nor the contraction curve to the thromboxane A2-mimetic, U46619. 4. Both the relaxation response to thimerosal and the selective block of the relaxation responses to stimulated EDRF release were unaffected by either indomethacin (10 microM) or superoxide dismutase (150 u ml-1). 5. L-NNA (100 microM) significantly blocked the relaxation curves to thimerosal and A23187 but not that to SNP.6. Abolition of stimulated EDRF-mediated responses with thimerosal was unlikely to result from maximal and maintained stimulation of EDRF release even when active U46619-induced force had returned to pre-thimerosal levels, since the relaxation curves to glyceryl trinitrate (GTN) and SNP were markedly attenuated in the presence of SNP and GTN respectively when active force was restored with endothelin-1 (ET-1).7. Melittin (1 microM), ionomycin (1 microM) and A23187 (1 microM) each had selective effects on stimulated but not basal EDRF responses, similar to those of thimerosal.8. We propose that stimulated but not 'basal' release of EDRF is dependent on the release of arachidonic acid or one of its non-cyclo-oxygenase metabolites, possibly by Ca2'-dependent activation of phospholipase A2.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1989

Hyposensitizing therapy with standard antigenic extracts: an important source of thimerosal sensitization.

The frequency of thimerosal sensitization was determined in 5 groups of subjects: military recruits; healthy subjects; patients with asthma or rhinitis undergoing hyposensitizing therapy with thimerosal-preserved antigenic extracts; patients with allergic contact dermatitis; patients with allergic contact conjunctivitis. Our patients with allergic contact dermatitis have a higher incidence of positive patch tests to thimerosal than healthy subjects. The source of thimerosal sensitization in this group remains obscure, their history of exposure to this or to other mercury derivatives being comparable to that of the healthy population. Patients with allergic contact conjunctivitis and patients receiving immunotherapy for asthma or rhinitis present a significantly higher frequency of thimerosal sensitization than the other groups, indicating that ophthalmic solutions and thimerosal-preserved allergen extracts are an important source of thimerosal sensitization. The clinical relevance of thimerosal sensitization was definitively established only in patients with allergic contact conjunctivitis, even though patients receiving immunotherapy frequently presented local reactions at the site of allergen inoculation.

Adult↗

PubMed1986

Thimerosal induces endothelium-dependent vascular smooth muscle relaxations by interacting with thiol groups. Relaxations are likely to be mediated by endothelium-derived relaxing factor (EDRF).

The sulfhydryl reagent thimerosal, as well as acetylcholine and Ca2+-ionophore A23187, produced concentration-dependent relaxations of intact rabbit aortic strips. The ability of strips to relax in response to these agents was dependent on the presence of vascular endothelium. Purposely removing the endothelium led to a complete loss of the relaxation responses. Thimerosal was at least as efficacious as A23187 in inducing endothelium-dependent relaxations, but its relaxations developed much slower than those induced by A23187 or acetylcholine. A small concentration of thimerosal that had no appreciable effect by itself, potentiated the relaxing response to acetylcholine in endothelium-intact preparations. Endothelium-dependent relaxations induced by larger concentrations of thimerosal, as well as relaxations produced by acetylcholine, were inhibited by the antioxidant and lipoxygenase inhibitor nordihydroguaiaretic acid, by haemoglobin, and by the inhibitor of soluble guanylate cyclase methylene blue. Indomethacin had no effect on these relaxations. The thiol compounds glutathione, 2-mercaptoethanol and a low concentration of dithiothreitol prevented (and reversed) relaxations induced by thimerosal, but had little or no effect on ACh relaxations. A high concentration of dithiothreitol also markedly inhibited the ACh relaxation. These results are consistent with the hypothesis that thimerosal stimulates endothelial cells to produce a relaxing substance whose properties are similar or the same as those of the endothelium-derived relaxing factor (EDRF) released in response to acetylcholine or A23187. The biochemical mechanism by which thimerosal induces the formation and/or release of this relaxing substance is likely to be different from ACh.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

PubMed1990

Involvement of calcium in the thimerosal-stimulated formation of leukotriene by fMLP in human polymorphonuclear leukocytes.

Only small amounts of leukotrienes could be detected by reverse-phase HPLC analysis after stimulation of human polymorphonuclear leukocytes (PMN) by the receptor agonist N-formyl-methionyl-leucyl-phenylalanine (fMLP). Preincubation of the cells with the organomercury compound thimerosal prior to fMLP-addition, however, resulted in the formation of significant amounts of 5-lipoxygenase derived metabolites. This effect was dose-dependent with respect both to fMLP and thimerosal. Thimerosal alone did neither lead to the formation of HPLC-detectable leukotrienes nor to the release of arachidonic acid in [1-14C]arachidonic acid prelabelled cells. The formation of leukotrienes by fMLP/thimerosal required extracellular Ca2+. Measurements of intracellular Ca2(+)-levels revealed that (i) thimerosal alone is able to release Ca2+ from internal stores and (ii) thimerosal causes a persistent accumulation of Ca2+ within the cells after stimulation by fMLP. We conclude that by the synergistic action of fMLP and thimerosal the Ca2(+)-levels exceed the threshold for phospholipase A2 activation resulting in the liberation of arachidonic acid and subsequently in the formation of 5-lipoxygenase products. Our results suggest that thimerosal may provide a model for leukotriene formation under pathophysiological conditions when SH-group oxidation leads to increased intracellular Ca2(+)-levels.

Arachidonate 5-Lipoxygenase↗

PubMed1992

The endothelium-dependent effects of thimerosal on mouse pial arterioles in vivo: evidence for control of microvascular events by EDRF as well as prostaglandins.

Thimerosal causes synthesis and/or release of both endothelium-derived relaxing factor (EDRF) and prostaglandins from conductance vessels in vitro. We tested its effects and mechanism of action on mouse pial arterioles in vivo using intravital microscopic techniques. Topical thimerosal dilated pial arterioles. This effect was eliminated by endothelial injury produced by a laser/Evans blue technique. Dilation was also eliminated by topical L-NMMA, a reported inhibitor of EDRF synthesis. Topical thimerosal also reduced the incidence of platelet adhesion/aggregation ("capture") at a site of minimal endothelial damage. This effect was eliminated by L-NMMA pretreatment. The ability of thimerosal to dilate arterioles was eliminated not only by treatments thought to eliminate synthesis/release of EDRF, but also by cyclooxygenase inhibitors. However, inhibition of platelet adhesion/aggregation was not affected by cyclooxygenase inhibition. Thimerosal significantly increased production of prostaglandin E2 recovered from a closed cranial window. We conclude that the dilating effects of thimerosal on diameter require two endothelium-derived agents: EDRF and one or more prostaglandins acting in concert. However, the inhibiting effect of thimerosal on local platelet adhesion/aggregation appears to be caused only by an increase in EDRF at the injured site.

6-Ketoprostaglandin F1 alpha↗

PubMed1991

Vaccination despite thimerosal sensitivity.

Thimerosal sensitivity is extremely common in Austria, being surpassed as a contact allergen only by nickel. This high incidence is still rising and is probably due to the frequent vaccinations which are performed in Austria. Most of the patch-test-positive patients had recently been immunized with thimerosal-containing vaccines, and no other obvious sources of exposure to thimerosal could be found. On retrospective questioning, 48 out of 50 patients had had no problems with their recent immunization; the 2 who reported massive local reactions had received their injections, against the recommendation of the manufacturer, subcutaneously. In a prospective study, 12 thimerosal-sensitized persons received their follow-up immunization at our department, and no side effects occurred. This enables us to conclude that sensitization had occurred through vaccines, but that those amounts of thimerosal delivered i.m. are not sufficient to elicit clinical symptoms. Patch-test positivity to thimerosal thus represents no contra-indication to i.m. immunization with thimerosal-containing vaccines.

Adolescent↗

PubMed1979

Human platelet aggregation by thimerosal. Functional and ultrastructural studies.

Thimerosal, a sulfhydryl group inhibitor, produces in an aggregometer a decrease in optical density of normal platelet-rich plasma over a wide range of concentrations. Ultrastructural study shows that the decrease of optical density produced by thimerosal at low doses is due to a true platelet aggregation preceded by a release reaction, whereas the aggregometric curves recorded after addition of thimerosal at high doses can be attributed to marked alterations of platelet morphology. Electron microscopic study shows the presence of electron-dense material between plasma membranes after addition of a low dose, and the early rupture of membranes after a high dose. These findings support previous conclusions that thimerosal binds to plasma membranes. Thimerosal induces a release reaction, seen in ultrastructural study and revealed by measurement of 14C-serotonin release. Moreover, thimerosal-induced aggregation is independent of released ADP and of formation of intermediates of the arachidonate pathway. Thimerosal-induced platelet aggregation is inhibited neither by ADP removal nor by aspirin addition.

Adenosine Diphosphate↗

PubMed1977

Effect of the ophthalmic preservative thimerosal on rabbit and human corneal endothelium.

Widespread use of the mercurial-containing preservative thimerosal as an antibacterial agent in ophthalmic drugs and solutions warranted an investigation into its possible cytotoxic effects on the functional and ultrastructural integrity of the corneal endothelium. No changes in corneal thickness were observed during 5 hours' perfusion of the endothelium of rabbit and human corneas with 0.0001 and 0.0005 percent thimerosal in glutathione bicarbonate Ringer's solution (GBR). Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) of the endothelium of the 0.0001 percent group revealed normal ultrastructure. SEM and TEM of the endothelium of corneas perfused with 0.0005 percent thimerosal for 5 hours revealed condensed mitochondria, cytoplasmic vacuoles, and cytoplasmic flaps at the apical end of the cellular junctions. Perfusion of higher concentrations (0.001 and 0.005 perecnt) of thimerosal in GBR resulted in increases in corneal thickness after 2 hours and irreversible ultrastructural damage to the endothelial cells by 5 hours. Corneas perfused with 0.01 and 0.1 percent thimerosal in GBR showed a rapid and immediate increase in corneal thickness and endothelial cell death and necrosis within 1 hour. It is postulated that the mercury in thimerosal becomes bound to the cell membrane protein sulfhydryl groups, causing an increase in cellular permeability; These results suggest that the prolonged exposure of the corneal endothelium to thimerosal in the accepted antimicrobial dosage of 0.005 to 0.001 percent may result in functional and structural damage to the endothelium.

Animals↗

PubMed1989

The sulfhydryl reagent thimerosal elicits human platelet aggregation by mobilization of intracellular calcium and secondary prostaglandin endoperoxide formation.

The effect of the sulfhydryl (SH) group inhibitor ethylmercurithiosalicylate (thimerosal) on the function of human platelets was investigated. In contrast to known SH reagents such as p-chloromercuribenzoate or N-ethylmaleimide, thimerosal elicited both aggregation and [3H]serotonin release of washed human platelets at low micromolar concentrations (greater than or equal to 2 microM). Only a significant higher dose (greater than or equal to 15 microM) was effective when platelets were pretreated with the cyclooxygenase inhibitor aspirin, indicating an amplification of the proaggregatory effect of thimerosal by secondary prostaglandin (PG) endoperoxide and/or thromboxane (TX) formation. Consistent with this notion, thimerosal induced endogenous platelet arachidonic acid (20:4) metabolism which could be attributed to enhanced 20:4 liberation, presumably by activation of phospholipase A2. The latter effect was mediated by mobilization of intracellular calcium (Ca2+), and was not affected by removal of extracellular Ca2+. In the presence of aspirin, the thimerosal-induced Ca2+ elevation was completely reversed by dithiothreitol (DTT) which implicates SH groups in intracellular Ca2+ transport. In contrast to previous observations with other SH reagents, thimerosal had no effect on the inositoltrisphosphate (IP3)-mediated release or the sequestration (and/or extrusion) of intracellular Ca2+ following stimulation with thrombin, indicating an action on an as yet undefined CA2+ transport system.

Aspirin↗

PubMedDate not supplied

Effect of thimerosal concentration on the efficacy of inactivated Newcastle disease oil-emulsion vaccines.

Different quantities of the preservative thimerosal in inactivated Newcastle disease oil-emulsion vaccines were tested to determine the influence on the hemagglutination-inhibition (HI) response of broilers. The effect of thimerosal was measured in vaccines that had been stored for 1, 21, and 52 weeks; HI serology was conducted at 2, 4, and 6 weeks after vaccination. Mean HI titers 4 weeks after vaccination decreased at a significant rate (P less than or equal to 0.001) with increasing concentrations of thimerosal. HI titers 4 weeks after vaccination with 1-week-old vaccine were significantly (P less than or equal to 0.05) higher than those after vaccination with 52-week-old vaccine at all thimerosal concentrations tested. Titers were also significantly higher (P less than or equal to 0.05) after vaccination with 1-week-old vaccine than after vaccination with 21-week-old vaccine at all thimerosal concentrations below about 8.25 mg/ml of antigen. Thimerosal at the levels recommended in commercial vaccines does not significantly decrease vaccine efficacy.

Animals↗

PubMed1976

Platelet aggregation by thimerosal: role of ADP and SH groups.

Thimerosal, a sulphydryl inhibitor, induces aggregation of normal platelet rich plasma over a wide range of concentrations. Low doses induce a monophasic response preceded by a lag phase, high doses produce an immediate biphasic response. Thimerosal induces platelet aggregation through its binding by sulphydryl groups. Thimerosal induced aggregation is not mediated by ADP, it is not influenced by fibrinogen, von Willebrand factor, calcium, and magnesium ions of the medium. Thimerosal induced platelet aggregation is normal in patients affected by thrombocytopathia (defect of ADP release) but not in patients affected by Glanzmann's thrombasthenia. Mercaptopropionglycine, a substance which tends to preserve SH groups, inhibits platelet aggregation induced by thimerosal, thrombin, collagen, and ADP. A mechanism is proposed for thimerosal induced aggregation and the role of SH groups also in ADP, thrombin and collagen induced aggregation is indicated.

Adenosine Diphosphate↗

PubMed1990

Thimerosal hyperpolarizes arterial smooth muscles in an endothelium-dependent manner.

Thimerosal activates the production of endothelium-derived relaxing factor (EDRF). I examined whether thimerosal also causes the release of an endothelium-dependent hyperpolarizing factor (EDHF). Thimerosal caused an endothelium-dependent hyperpolarization of smooth muscle. This effect is unlikely to be caused by the property of thimerosal to inhibit the acyl-coenzyme A: lysolecithin acyltransferase (LAT) since neither arachidonic acid nor lysolecithin hyperpolarized the muscles. I conclude that thimerosal is not a pure activator of EDRF (nitric oxide) production, but that it also releases a distinct EDHF.

1-Acylglycerophosphocholine O-Acyltransferase↗