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T Thorsen

Publications and source records attributed to T Thorsen.

At least 37 records · Page 2Linked to original sources
PubMed1993

Microbubble-induced phospholipase C activation does not correlate with platelet aggregation.

The effect of nitrogen-(N2-)microbubbles on platelets resembles that of common platelet agonists with respect to aggregation and secretion, but is considerably slower and is poorly inhibited by aspirin. This paper reports the effect of microbubbles on platelet phospholipase C activity in gelfiltered human platelets prelabelled with [32P]Pi ([32P]-GFP). The experiments were run in the presence of an ADP scavenging system in order to rule out effects of ADP. Stimulation of [32P]-GFP for 30 min with microbubbles caused a significant reduction in single platelets (p < 0.0004) and a significant increase in 32P-activity in the phosphatidic acid (PA) fraction (p < 0.02). Epinephrine potentiated the microbubble-induced reduction in single platelets (p < 0.05), but did not enhance the amount of 32P in the platelet [32P]PA fraction. The 32P-radioactivity in the PI-fraction increased with time to a similar extent when [32P]-GFP was stirred for 30 min in absence of microbubbles as it did after 30 min of agonist exposure. There were no significant changes in the [32P]PIP and [32P]PIP2 fractions. Aspirin abolished the microbubble-induced increase in 32P-activity in the PA fraction, but had no significant effect on the reduction in single platelets. Aspirin had a small but significant, reducing effect on platelet aggregation induced by a combination of epinephrine and microbubbles (p < 0.05). With epinephrine, however, aspirin did not completely abolish the increase in [32P]-PA. It is concluded that microbubbles alone cause platelets to aggregate by a novel mechanism that operates independent of cyclooxygenase-dependent arachidonic acid metabolites and phospholipase C activation.

Aspirin↗
PubMed1993

Bubble-induced aggregation of platelets: effects of gas species, proteins, and decompression.

We show that bubbles containing different gases (N2, He, Ne, Ar, or an O2-CO2-N2 mixture) are equally potent platelet agonists. The synergistic effect of different platelet antagonists does not seem to be affected by the type of gas in the bubbles. In contrast to aggregation in platelet-rich plasma (PRP), bubbles cause only a weak response in gel-filtered platelets (GFP), i.e., comparison of aggregation in protein-rich and protein-poor platelet suspensions may shed light on the role of different plasma proteins. Extracellular fibrinogen promotes bubble-induced platelet aggregation similar to known physiologic agonists, whereas albumin counteracts this aggregation. Bubble-induced aggregation is inhibited in GFP-fibrinogen by 2-deoxy-D-glucose plus antimycin A, suggesting dependency on ATP generation in the platelets and evidence for direct exposure of the "cryptic" fibrinogen receptor by bubbles. Hyperbaric compression and subsequent rapid, inadequate decompression of PRP caused little change in the aggregation response to gas bubbles and epinephrine at 1 bar, but reduced the response to ADP. Bubbles tended not to form before the surface film was broken. Pressure-induced aggregation was apparently metabolically active and not due to passive agglutination; electron microscopic studies and PRP with added glutaraldehyde did not show platelet activation, clumping, or reduced platelet count. In contrast to aggregation caused by pressure, bubble-induced aggregation in PRP at 1 bar (after treatment in the pressure chamber) was nearly completely inhibited by theophylline, a phosphodiesterase inhibitor that increases intracellular platelet cyclic AMP.

Adenosine Diphosphate↗
PubMed1992

Oestradiol treatment increases the sensitivity of MCF-7 cells for the growth stimulatory effect of IGF-I.

MCF-7 cells were grown in serum free medium (Dulbecco MEM without phenol red, supplemented with Costar SF-1 without insulin). Insulin was added as required and gave dose dependent growth stimulation at concentrations between 5 and 10,000 nM. Identical growth response curves were obtained for thymidine uptake and cell number. Oestradiol and insulin-like growth factor I (IGF-I) added individually both gave a dose dependent stimulation of cell growth in serum free medium containing 50 nM insulin. The growth stimulatory effect of oestradiol was to a large extent inhibited with suramine, a general inhibitor of growth factors, indicating that the effect of oestradiol was mediated through stimulating autocrine secretion of a growth factor. To investigate a possible link between the effects of oestradiol and IGF-I, a specific IGF-I receptor antibody (alpha IR-3), 10 micrograms/ml was used. These experiments were carried out with 2.5 nM insulin in the medium, a concentration at which insulin had no growth stimulatory effect. Stimulation was carried out for 18 h before assay of thymidine uptake. The effect of oestradiol was not significantly reduced by alpha IR-3, indicating that IGF-I was not an autocrine mediator of oestradiol stimulation of cell growth under these conditions, whereas alpha IR-3 extensively reduced growth stimulation by IGF-I. On long term stimulation (5 days) oestradiol had a marked stimulatory effect on cell number and alpha IR-3 almost totally abrogated this effect. When oestradiol (1 nM) and IGF-I (2.5 nM) were added together, the combined effect on thymidine incorporation and cell number was significantly greater than additive. This synergistic effect on the IGF-I growth response was totally abolished by the IGF-I receptor antibody. The results suggest a cooperative interaction of oestradiol and IGF-I. It is concluded that growth stimulation of MCF-7 cells by long term treatment with oestradiol may be mediated through autocrine secretion of IGF-I. the effect of short term stimulation of thymidine incorporation suggest that the growth response of oestradiol is more complex, and indicate that a cooperative interaction with IGF-I is involved, which is unrelated to stimulated autocrine secretion.

Antibodies↗
PubMed1992

Porcine platelets in vitro and in vivo studies: relevance to human thrombosis research.

This review summarizes present knowledge on porcine platelets in vitro and recent studies on in vivo activation of platelets in the pig. There are certain differences compared to human platelets: Platelet aggregation and secretion cannot be achieved by epinephrine, and the arachidonate pathway seems poorly developed in porcine platelets. Genetic models for von Willebrand disease (vWD) and storage pool deficiency (SPD) have been developed in the pig. Several models for the study of in vivo platelet deposition and early thrombus formation have been developed. Platelet radio-labeling techniques (with 111In) have been used extensively. We conclude that the pig seems to be a good choice for the investigation of in vivo platelet activation and deposition based on present knowledge of porcine platelets and on already established animal models.

Angioplasty, Balloon↗
PubMed1992

Effects of hyperoxia on human endothelial cell proliferation and morphology in vitro.

The effects of hyperoxia on endothelial cells from human umbilical veins were studied in vitro by flow cytometric DNA analysis, cell proliferation, and morphology. Exposure of the cells to PO2 of approximately 400 and 500 mmHg (corresponding to O2 concentrations of 65 and 95%, respectively) caused, after 24 h, an increase in the proportion of S-phase cells from 18 to 33%. This was followed by a dramatic decrease of S-phase cells to about 4% after 48 h of O2 exposure. This decrease was also sustained after 72 h of O2 treatment. Concomitant with the depletion of S-phase cells was an increase from 13 to 21% in the proportion of cells in the G2M phase, indicating that cells were unable to undergo cell division after a 48-h exposure to 65 and 95% O2. Cells exposed to various PO2 levels (124, 248, 400, and 500 mmHg) showed a dose-dependent reduction in cell proliferation leading to a total inhibition of cell growth after exposure to PO2 of 400 and 500 mmHg. Cells exposed to 248 mmHg PO2 exhibited similar growth rates as the control cells during the first 3 days. Thereafter there was a 50% reduction in cell density as compared to the control cells. Light and scanning electron microscopy showed that the hyperoxic cells underwent morphologic changes characterized by cell contraction and swelling. Thus it is shown that exposure to very high PO2 tensions first stimulates the cells to enter the S phase of the cell cycle. Thereafter changes take place leading to a nearly complete reduction of cell proliferation.

Cell Count↗
PubMed1991

Microbubble-induced serotonin secretion in human platelets.

The effect of nitrogen (N2) microbubbles on platelets resembles that of common platelet agonists with respect to aggregation (Thorsen T et al., Undersea Biomed Res 1986; 13: 289-303). In the present study we examined the effect of microbubbles on platelet secretion of preloaded 14C-serotonin. We demonstrate that stirring of platelet-rich plasma with N2-microbubbles causes a loss of single platelets that is associated with secretion. However, secretion did not increase above baseline values until after 20 min of microbubble exposure, when platelet aggregation had reached 40%. After that time the secretion rate increased. There was no correlation between secreted serotonin and the degree of platelet aggregation. Although no 14C-serotonin secretion occurred in presence of acetylsalicyclic acid (ASA), microbubble-induced platelet aggregation was only marginally reduced. Epinephrine alone caused significant platelet aggregation but no 14C-serotonin secretion and it enhanced N2-microbubble-induced platelet aggregation and secretion; ASA completely prevented secretion under these circumstances but failed to abolish the enhancement of aggregation compared with microbubbles alone. Earlier studies have shown that platelets adhere to the bubble surfaces (Thorsen T et al., Undersea Biomed Res 1987; 14: 45-59). The results in the present study indicate that non-adhering platelets in the bulk phase are not activated by means of autocrine stimulation through dense granule material.

Blood Platelets↗
PubMed1990

Growth control of human mammary cancer cells (MCF-7 cells) in culture: effect of estradiol and growth factors in serum-containing medium.

The growth control of estrogen-dependent mammary cancer is very complex and only partly understood. The present study was undertaken in order to establish conditions for growth control of MCF-7 cells in monolayer culture with focus on the effect of estradiol-17 beta, fetal calf serum, and growth factors. The effect of charcoal-stripped fetal calf serum (CSFCS) on cell growth was dependent upon the presence of hormones or growth factors in the medium. In the presence of insulin (or insulin-like growth factor 1) and in the absence of estradiol-17 beta, increasing concentrations of CSFCS, 0.625-20%, produced a bell-shaped growth response curve. Serum concentrations greater than 2.5% inhibited cell growth in the absence of estradiol-17 beta, whereas CSFCS in a dose-dependent way up to 10% stimulated growth in the presence of estradiol-17 beta (5 x 10(-10) mol/liter). The growth inhibitory effect of CSFCS could not be demonstrated in the absence of insulin (or insulin-like growth factor 1) and estradiol-17 beta. CSFCS stimulated growth in a dose-dependent way in the presence of estradiol-17 beta and also in the absence of insulin. Both the putative growth inhibitor and stimulator were found to be heat stable and not dialyzable. Epidermal growth factor stimulated growth but was unable to eliminate the growth inhibitory effect of 5-10% CSFCS. Interleukin-1 alpha inhibited MCF-7 cell growth in a dose-dependent way and produced a 75% reduction in cell number at a concentration of 5 x 10(-10) mol/liter. This inhibition was almost totally overcome by estradiol-17 beta. It is concluded that serum appears to contain factors with both stimulatory and inhibitory effects on the growth of MCF-7 cells. The inhibitory effect can be eliminated by estradiol (5 x 10(-10) mol/liter). In the presence of estradiol cell growth is stimulated by CSFCS in a dose-related way up to 5-10%. Taken together these data seem to indicate that estradiol stimulates cell growth in two principal ways: partly by eliminating the effect of an inhibitor, in support of a "negative hypothesis," and partly by an effect whereby estradiol permits a growth stimulator in CSFCS to be expressed, in support of the "indirect positive hypothesis."

Breast Neoplasms↗
PubMed1990

Phosphorylation of the estradiol receptor in MCF-7 human breast cancer cells in culture.

Double labelling and Western blot techniques were used to demonstrate phosphorylation of estradiol receptor. Cells in monolayer culture were incubated with [32P]orthophosphate for 18 h followed by covalent whole cell labelling of the estradiol receptor with tritiated tamoxifen aziridine [( 3H]TA). Labelled receptor was precipitated with the monoclonal antibodies H222 or JS 34/32, coupled to protein A-Sepharose, and purified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), or transferred to nitrocellulose paper. Receptor protein was detected on the Western blot with the monoclonal antibody H222 and rabbit anti-rat peroxidase conjugate. Phosphorylated receptor was visualized by autoradiography. Tritium and 32P activities were monitored in the gels. Two phosphorylated forms of the receptor (molecular weights 67 and 50 kDa) have been detected in MCF-7 cells. Estradiol treatment of the cells was found to increase phosphorylation of the receptor. In estradiol-treated cells both phosphorylated receptor forms were present mainly in the nuclear extract. Both forms bound [3H]TA as evidence by SDS-PAGE. [3H]TA binding was abolished by excess non-radioactive estradiol. In addition two phosphorylated proteins of approximately 120 and 90 kDa were regularly coprecipitated with receptor in cytosol. These proteins did not bind [3H]TA. The 90 kDa phosphorylated protein was identified as a heat shock protein (hsp-90).

Blotting, Western↗
PubMed1990

Estradiol increases phosphorylation of the 90 kDa heat shock protein not associated with estradiol receptor in MCF-7 cells in culture.

MCF-7 cells in monolayer culture were incubated with [32P]orthophosphate for 18 h followed by covalent whole cell labelling of the estradiol receptor with tritiated tamoxifen aziridine [( 3H]TA). The heat shock protein (hsp-90) bound to receptor was precipitated with monoclonal antibodies H222 or JS 34/32, coupled to protein A-Sepharose and purified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) under reducing conditions. Hsp-90 not associated with receptor was similarly purified after isolation with the monoclonal antibody AC88. It was found that estradiol treatment of the cells markedly increased phosphate incorporation in the free hsp-90, without affecting heat shock protein bound to receptor. A 6-fold increase in phosphate content was observed after 10 min incubation of the cells with estradiol. A similar effect was seen after treatment of the cells with the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA). The calcium ionophore A23187 had no influence on hsp-90 phosphorylation, and treatment of the cells with forskolin to increase the cellular content of cAMP had a reverse effect. A 50% reduction of the phosphate content in the free hsp-90 was observed after 15 min treatment. The observation that estradiol, TPA and forskolin had effect only on hsp-90 not bound to receptor is an indication that the receptor-hsp-90 complex exists in vivo. Time course studies show that the effect of estradiol is non-genomic. Two possible explanations of the results seem to exist. Either estradiol induces an increase in the degree of phosphorylation of hsp-90, or hsp-90 is translocated to the cytosol from a different cellular compartment.

Blotting, Western↗
PubMed1990

Effect of ATP on the regulation of the steroid binding activity of the oestradiol receptor.

We have observed that ATP induces a second type of oestradiol binding site with slightly lower affinity (Ka 3.3 x 10(8) M-1) and lower sedimentation coefficient (4 S) in cytosol from immature lamb uterus and MCF-7 cells. A factor isolated from immature lamb uterine nuclear extract was found to decrease the steroid binding activity of oestradiol receptor that had been purified by heparin Sepharose and oestradiol-Sepharose chromatography. Inhibition of this factor by known phosphatase inhibitors, indicated that this factor may be a phosphatase. Another factor isolated from immature lamb uterine cytosol was found to enhance the effect of ATP on receptor binding in cytosol from immature lamb uterus and MCF-7 cells. The ability of this factor to phosphorylate a partially purified cytosol receptor from immature lamb uterus when incubated with [gamma 32P]ATP, indicates that this factor is a phosphokinase. The phosphorylated products after labeling with [3H]tamoxifen aziridine were characterized by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. Three phosphorylated proteins with molecular weights 150, 97, and 67 kDa bound [3H]tamoxifen aziridine. Ammonium sulphate precipitated cytosol oestradiol receptor from immature lamb uterus was inactivated with receptor inactivating factor and then reactivated with receptor activating factor in the presence of [gamma 32P]ATP and substantially affinity labelled with [3H]tamoxifen aziridine. The affinity labelled oestradiol receptor was immunopurified with the monoclonal antibody JS 34/32. Three proteins with molecular weights 67, 50 and 43 kDa specifically bound [3H]tamoxifen aziridine and only 43 kDa receptor fragment was phosphorylated. The relevance of inactivation/reactivation of oestradiol receptor to the dephosphorylation/phosphorylation of receptor is discussed.

Adenosine Triphosphate↗
PubMed1989

Improved measurement of androgen receptors in human breast cancer.

Molybdate-stabilized androgen receptors have been quantitated in cytosols derived from 1026 malignant breast tumors including all new cases of primary breast cancer reported in the western region of Norway during the 3-year period 1985-1987. A simple single point saturation assay using the synthetic labeled ligand methyltrienolone was evaluated for this purpose. This approach also allowed the simultaneous determination of estrogen and progesterone receptor from the same cytosol preparation. The cytosol content of albumin was also recorded in order to control for dilution by extracellular proteins. Androgen receptor was the sex hormone receptor most frequently found both in primary and secondary breast cancer. In primary tumors 84.9% (723 of 852) showed a cytosol concentration higher than 10 fmol/mg protein compared to 71.2 and 67.1% for estrogen and progesterone receptors, respectively. This incidence is about 2 times higher than previously reported for androgen receptors in the literature and may be due to the stabilizing effects of molybdate and a serine protease inhibitor on the recovery of active binding sites in cytosol. Cytosol concentration of androgen receptor is generally lower than that of the other sex hormone receptors; the average level was 65.5 fmol/mg cytosol protein compared to 86.8 and 84.7 for estrogen and progesterone receptors, respectively. Both incidence and cytosol concentrations were lower for all sex hormone receptors in soft tissue metastasis than in the primary tumor. This decrease is not likely to be due to differences in tumor cellularity since metastatic tumors appear to be more cellular as judged from a lower cytosol content of extracellular proteins (albumin). No significant differences were observed in any parameter investigated between different metastatic sites (skin, lymph nodes). Androgen receptor levels were strongly correlated to estrogen and progesterone receptor concentration in both primary and secondary cancers. Cytosol androgen receptor concentration increases with age. This increase is more significant in metastatic than in primary tumors. Evidently, tumor cellularity is a confounding factor in primary tumors since tumor cytosols from younger patients showed a higher content of extracellular proteins. Receptor levels in lymph node metastasis did not exhibit age dependence. This may suggest that locally produced factors rather than circulating levels of sex steroids modulate tumor receptor expression. In metastatic tissues androgen receptors are present with twice the frequency of progesterone receptors and one in four of these tumors express androgen receptor as their sole sex hormone receptor. This supports the view that some of the beneficial effects of high dose progestin treatment of advanced breast cancer are mediated through the androgen receptor.(ABSTRACT TRUNCATED AT 400 WORDS)

Breast Neoplasms↗
PubMed1989

Separation of urinary metabolites of radiolabelled estrogens in man by HPLC.

A method to separate radiolabelled urinary estrogens by high performance liquid chromatography (HPLC) is described. Estrogen glucuronides were isolated from the urine of women receiving bolus injections of [4-14C]estrone or [4-14C]estradiol by adsorption on Sep-Pak C18 cartridges and subsequent DEAE Sephadex A25 column chromatography. Following enzyme hydrolysis, free estrogens were extracted and concentrated in methanol-water containing ascorbic acid. HPLC was performed either by C18 reversed phase chromatography using different concentrations of acetonitrile with or without tetrahydrofurane in phosphate buffer or methanol-water as mobile phases, or on a Diol column using chloroform-isooctane-n-hexane or isopropanol-isooctane-n-hexane as mobile phases. 3H-labelled estrogens were added as internal standards, and urinary [14C]estriol, [14C]estradiol and [14C]estrone concentrations could be measured with an interassay coefficient of variation less than 5%. Interassay coefficients of variation for [14C]2-hydroxyestriol, [14C]16 alpha-hydroxyestrone, [14C]2-hydroxyestradiol, [14C]2-hydroxyestrone and [14C]2-methoxyestrone were between 5 and 10%, while interassay coefficients of variation for [14C]4-hydroxyestrone was 14.6%. Recovery of the unstable catechol estrogen 2-hydroxyestrone was comparable to the recovery of the other estrogen metabolites, due to the addition of ascorbic acid throughout the different pre-chromatographic steps. Our method is suitable for the separation of the major labelled estrogen metabolites found in human urine following administration of radiolabelled estrone or estradiol.

Aminoglutethimide↗
PubMed1989

Effects of aminoglutethimide on plasma estrone sulfate not caused by aromatase inhibition.

Plasma levels of estrone and estrone sulfate were measured in 16 postmenopausal women with advanced breast cancer before and during chronic aminoglutethimide therapy. Aminoglutethimide caused a significant reduction in plasma estrone (mean 36%, P less than 0.025) and estrone sulfate (mean 65%, P less than 0.001). The estrone/estrone sulfate ratio was increased by a mean of 84% (P less than 0.0025). These results suggest that aminoglutethimide influences plasma estrone sulfate by mechanisms unrelated to aromatase inhibition. The findings in this study are consistent with previous results suggesting that aminoglutethimide treatment enhances the rate of estrone sulfate metabolism. This biochemical effect of aminoglutethimide treatment could be a contributory factor to the drugs mechanism of action.

Adult↗
PubMed1989

Plasma levels of estradiol, estrone, estrone sulfate and sex hormone binding globulin in patients receiving rifampicin.

Plasma estrone, estradiol, estrone sulfate, androstenedione, testosterone and sex hormone binding globulin were measured in 14 patients (3 postmenopausal women, 11 men) with tuberculosis who received rifampicin. During treatment a moderate, but significant increase in the plasma level of estradiol (mean increase 32%, P less than 0.01) and estrone (mean increase 13%, P less than 0.01) were seen. In contrast, plasma estrone sulfate was significantly reduced (mean reduction of 25%, P less than 0.05). No alteration in plasma testosterone was observed, but there was a slight (mean 15%) increase in plasma androstenedione of borderline significance (P = 0.052). In eight patients, from whom all tuberculostatic treatment except rifampicin had been withdrawn, plasma sex hormone binding globulin was found to be increased by 75% by rifampicin treatment. Further, the results obtained in this part of the study confirmed the alteration in plasma estrone sulfate to be caused by rifampicin alone without any contribution from other tuberculostatic drugs. While plasma estradiol could be increased due to elevation of sex hormone binding globulin, plasma estrone was probably increased secondary to the increase in plasma androstenedione. A reduced plasma estrone sulfate level suggests that rifampicin enhances the rate of estrone sulfate metabolism. The possibility that treatment with drugs which reduce plasma estrone sulfate might be beneficial for hormone dependent cancers is discussed.

Adult↗
PubMed1989

The prognostic role of progesterone receptor status and age in relation to axillary node status in breast cancer patients.

The prognostic role of axillary lymph node status, progesterone receptor (PgR) status, age of the patient at operation, oestrogen receptor (ER) status and tumour diameter was studied in 443 breast cancer patients treated by modified radical mastectomy. Logistic and proportional hazard regression analyses were used to estimate the prognosis from the time of operation up to 60 months. We also estimated the prognosis from 36 to 60 months for those who had survived 36 months (conditional analysis). PgR and age gave significant information in each node class, old age and PgR negativity being disadvantages. PgR status relative to node status was more important for estimating early (24 months) prognosis, while age was of more importance later (60 months). Node status and age were the only variables giving significant information in the conditional analyses. It is thus of importance to consider the time dependency of the prognostic variables when predicting survival in breast cancer patients. No effect was found for ER status or tumour diameter.

Age Factors↗
PubMed1989

Alterations in the production rate and the metabolism of oestrone and oestrone sulphate in breast cancer patients treated with aminoglutethimide.

Plasma level, plasma clearance, production rate and interconversions of oestrone and oestrone sulphate were measured in six breast cancer patients receiving aminoglutethimide therapy. Three additional patients had the production rate of oestrone sulphate investigated. Plasma oestrone and oestrone sulphate levels were reduced by a mean of 46% (P less than 0.05) and 71% (P less than 0.005) respectively. These alterations were due to a combined action of aminoglutethimide inhibiting oestrogen production but also increasing oestrogen metabolism. While oestrone and oestrone sulphate production rate was reduced by a mean of 31% (P less than 0.05) and 41% (P less than 0.005) respectively, the plasma clearance rate of oestrone was found to be increased by a mean of 30% (P less than 0.05), and the plasma clearance rate of oestrone sulphate was increased by a mean of 112% during aminoglutethimide treatment. The fraction of oestrone sulphate converted into plasma oestrone was reduced by 52% (P less than 0.05), the transfer of circulating oestrone into sulphate was non-significantly reduced by a mean of 16%. The findings in this investigation show that aminoglutethimide treatment influences oestrogen disposition by mechanisms unrelated to aromatase inhibition. The possibility that such effects might be partly responsible for the mechanism of action of aminoglutethimide in advanced breast cancer should be considered.

Aged↗
PubMed1989

Induction of platelet aggregation in vitro by microbubbles of nitrogen.

Microbubbles of nitrogen gas act as a platelet agonist, but the biochemical mechanisms involved in bubble-induced platelet activation are not well known. One characteristic property of a platelet agonist is to potentiate the response by another agonist in a synergistic manner at low concentrations. Possible synergism between N2 gas bubbles and the physiologic agonists ADP, epinephrine, and 5-hydroxytryptamine (5-HT) was tested. The interaction with ADP was additive; N2 microbubbles and ADP had different aggregation profiles, and the bubbles made the reversible ADP aggregation irreversible. Epinephrine caused a strong, synergistic stimulation of bubble-induced platelet aggregation. This synergism was only partially inhibited by indomethacin and acetylsalicylic acid, but abolished by yohimbine. 5-HT had an inhibitory effect on N2 microbubble-induced platelet aggregation. This effect was neutralized by the S2-serotonergic receptor blocker ketanserin. Microbubble stimulation of the platelets before stimulation with ADP, epinephrine, and 5-HT seemed to make them more sensitive to epinephrine only. The strong synergism between microbubbles and epinephrine in vitro should be evaluated for possible future use in predive selection of divers.

Adenosine Diphosphate↗