Biomedical subjects

V Quemener

Publications and source records attributed to V Quemener.

At least 19 recordsLinked to original sources

PubMed1996

Pretherapeutic erythrocyte polyamine spermine levels discriminate high risk relapsing patients with M1 prostate carcinoma.

BACKGROUND: Androgen deprivation is currently the standard treatment for patients with metastatic prostate carcinoma. Few reliable prognostic markers are able to select, at diagnosis, patients who will respond favorably and durably to hormone ablation. Circulating polyamines, markers of cell proliferation that are elevated in prostate carcinoma, have been evaluated as a prognostic tool. METHODS: Eighty-eight patients with untreated, M1 classified prostate carcinoma who received endocrine therapy between 1988 and 1993 were included in this study. Performance status, hemoglobin, alkaline phosphatases, prostate specific antigen, Gleason tumor grade, extent of disease by bone scan, and circulating erythrocyte spermidine and spermine were correlated with observed progression free and cause-specific survivals. Multiple correspondence analysis and ascending hierarchical classification were performed to determine significant pretreatment prognostic factors. RESULTS: Pretreatment performance status, alkaline phosphatase, hemoglobin, and erythrocyte spermine levels were correlated with progression, with hemoglobin and erythrocyte spermine level being the most significant independent variables (P < 0.00001 and P < 0.0001, respectively). With regard to cause specific survival, only hemoglobin and spermine erythrocyte levels were significant independent variables (P < 0.0001 and P < 0.0005, respectively). Patients with spermine levels of less than 9 nmol/8.10(9) had a statistically better outcome than patients with 9 nmol/8.10(9) or more erythrocytes. Erythrocyte spermine was the best sole determinant of progression. A test combining spermine with performance status or hemoglobin improved each variable's predictive values. CONCLUSIONS: Circulating erythrocyte spermine levels, extracted from a blood sample, can discriminate, at diagnosis, patients with hormone-refractory from those with hormone-responsive metastatic prostate carcinoma.

Aged↗

PubMed1996

In vivo, synergestic inhibition of MAT-LyLu rat prostatic adenocarcinoma growth by polyamine deprivation and low-dose cyclophosphamide.

Polyamine deprivation in vivo produces significant tumor growth inhibition of the hormone-resistant, metastatic Dunning Mat-LyLu murine prostatic carcinoma. In order to produce a cytotoxic effect in addition to the cytostatic effect of polyamine deprivation, various chemotherapy regimens, combined with drug-containing polyamine-deficient chow (DC-PDC), were assessed. Triple chemotherapy combining methotrexate, cyclophosphamide and vindesine; and monochemotherapy with high-dose cyclophosphamide (90 mg. kg-1) and low-dose cyclophosphamide (20 mg.kg-1) were studied alone and in combination with DC-PDC. A variant of DC-PDC excluding the polyamine oxidase inhibitor MDL 72527 was also studied in combination with low-dose cyclophosphamide. The triple-chemotherapy regimen alone or in combination with polyamine deprivation was effective on tumor growth inhibition but was also toxic. High-dose cyclophosphamide alone produced significant tumor growth inhibition and an increase in life span. High-dose cyclophosphamide in combination with DC-PDC was also effective on tumor growth but was also toxic. Low-dose cyclophosphamide alone was moderately effective on tumor growth inhibition with a marginal increase in life span. When combined with polyamine deprivation, results with low-dose cyclophosphamide compared favourably with those of high-dose cyclophosphamide alone and prevented the formation of lung metastases. The polyamine oxidase inhibitor does not appear to be mandatory to achieve this effect if DC-PDC is combined with low-dose cyclophosphamide. Polyamine deprivation appears to be an important tool in anticancer therapy, allowing the use of reduced doses of cytotoxic agents with the same antitumoral efficacy.

Adenocarcinoma↗

PubMed1996

Red blood cell polyamines, anaemia and tumour growth in the rat.

In rats with Mat Lylu prostatic carcinoma, significant changes in blood composition and red blood cell (RBC) characteristics were observed. Anaemia, characterised by a decrease in the number of RBC and the reduction of haemoglobin and the iron content in plasma, was correlated with tumour size and the accumulation of spermidine and spermine in the RBC. In large tumours, spermidine levels were increased by 8-fold over normal value. Spleen weight and splenic spermidine concentrations were enhanced in animals with tumours. After splenectomy, the rate of tumour growth decreased by 30%. It is proposed that anaemia in tumour-bearing animals is caused by enhanced RBC lysis, owing to the alteration of the rheological properties of RBC. These may be caused by the alterated surface characteristics due to polyamine accumulation. RBC lysis and high concentrations of polyamines in RBC and spleen appear, not only to favour tumour growth, but also to compromise the immunological defence mechanisms against neoplastic invasion.

Anemia↗

PubMed1996

Observations with an S-adenosylmethionine decarboxylase inhibitor in rats with prostatic adenocarcinoma.

CGP 48664A (2-(4-aminoiminomethyl)-2,3-dihydro-1H-inden-1-ylidene dihydrochloride, CAS 149400-88-4) is a new potent inhibitor of S-adenosylmethionine decarboxylase with antitumor properties. In view of the eminent clinical problems in the treatment of non hormone dependent prostatic cancer, the antiproliferative potency of this compound was tested in Dunning MAT-LyLu rat prostatic adenocarcinoma. The compound proved inefficient in preventing the growth of this tumor, even at a near toxic dose. A reason for the lacking effect is presumably the inadequate accumulation of the drug in the tumor cells due to the excessive growth rate of the MAT-LyLu xenografts. Tumor growth seems not to be accompanied by a proportionally rapid vascularization of the tumor mass. CGP 48664A was found to be a potent inhibitor of polyamine oxidase. This property of the drug may have contributed to the activation of the phagocytic capacity of peritoneal macrophages from tumor-bearing rats.

Adenocarcinoma↗

PubMed1995

Differential recognition of free and covalently bound polyamines by the monoclonal anti-spermine antibody SPM8-2.

The reactivity of an anti-spermine MAb (SPM8-2) toward polyamines either free or bound to a solid surface was investigated using equilibrium dialysis and ELISA methods. When polyamines were covalently linked to hydrophilized microtiter plates using carbodiimide, the MAb SPM8-2 reacted both with spermine and spermidine, with a higher affinity for the latter, but did not show any reactivity towards bound putrescine. In contrast, the MAb SPM8-2 reacted with all three polyamines bound to the microtiter plates with glutaraldehyde, with an affinity in the order: putrescine > spermidine > spermine. Equilibrium dialysis and competitive ELISA tests showed that the MAb SPM8-2 exhibited high affinity for free spermine and 50% and 5% cross-reactivity with free spermidine and putrescine respectively. The affinity of the MAb SPM8-2 for putrescine, spermidine and spermine appears to depend on whether the polyamine is free or bound. The antigenicity of the polyamines differs according to the nature of their link to the solid phase. These observations are discussed in the light of the structural modification produced by covalent binding of the polyamines. It is also concluded that when antibodies are used, due care has to be exercised in choosing the appropriate immunoassay for determining the specificity of antibodies directed against small haptens such as the polyamines.

Animals↗

PubMed1995

Erythrocyte polyamine levels: an indication of successful engraftment of bone marrow in children.

We studied the evolution of erythrocyte polyamine levels after 17 autologous bone marrow transplants (BMT) in 16 children with malignant diseases. We found that the time to the end of aplasia (0.5 x 10(9) granulocytes per liter) could be divided into 2 distinct periods. The first is characterized by low erythrocyte spermidine (Spd) and spermine (Spm) levels; the second is characterized by normal levels of polyamines. Spd and Spm levels were correlated (r = 0.74) during the second period, but not during the first period or in the control group. Furthermore, the time when Spd concentration was > or = 7 nmol/8 x 10(9) erythrocytes (19 +/- 7) was correlated (r = 0.64) with the advent of end of aplasia (30 +/- 10). We found no correlation between the numbers of CFU-GM and duration of aplasia levels or the duration of period A. The establishment of normal erythrocyte spermidine levels is the earliest index of successful marrow engraftment.

Adolescent↗

PubMed1994

Alterations in intestinal uptake of putrescine and tissue polyamine concentrations in tumor-bearing rats.

Intestinal absorption of putrescine and tissue metabolism of polyamines were investigated in rats grafted with the rapidly growing Mat-Lylu prostatic tumor. These animals exhibited a dramatic 21% decrease in weight and protein, but not DNA, content of their intestinal mucosa, relative to healthy rats reared under similarly controlled nutritional conditions. No significant variation in the specific activities of intestinal brush-border membrane enzymes was observed, however, suggesting a comparable differentiation state of intestinal cells exists in both groups. Putrescine uptake by brush-border membrane vesicles prepared from cancerous or healthy rat intestine was a time dependent process at 25 degrees C. Equilibrium uptake was much greater than could be explained by equilibration of the vesicle space with putrescine, indicating that the diamine was bound to membrane sites. Kinetics of putrescine uptake at 2 min revealed that the process involves two components, a saturable Michaelis-Menten carrier and passive diffusion. With respect to the kinetic parameters of putrescine transport, no significant changes were observed between the tumor-bearing and the control rats. After correction for nonspecific binding to the membranes, putrescine accumulation at equilibrium (75 min) was concentration-dependent and fit a single-site saturable model. Maximum accumulation of the diamine at equilibrium (Bmax) was increased by more than 46% in the cancerous rats relative to the controls, but the dissociation constant (Kd) was unchanged. Efflux of putrescine from the vesicles was slightly slower in the tumor-bearing group, but the differences were generally not significant. No change was observed with respect to the specific activity of ornithine decarboxylase and the concentration of polyamines in the intestinal mucosa. In Mat-Lylu grafted rats fed a standard diet supplemented with [14C]putrescine, about 19% of body radioactivity was recovered in the tumor within 24 h. This was concomitant with a decrease in the percentage of radioactivity retained in the intestinal, renal and hepatic tissues, relative to that retained in the same tissues of healthy rats. Our findings indicate that the presence of the tumor evolves an adaptive response in the small intestine of the rat, involving an increased capacity of the brush-border membrane to accumulate putrescine.

Adenocarcinoma↗

PubMed1994

Erythrocyte polyamines and prognosis in stage D2 prostatic carcinoma patients.

We studied 43 patients with newly diagnosed, untreated, stage D2 prostatic carcinoma, and correlated the initial performance status, hemoglobin, prostate specific antigen levels, tumor Gleason grade, extent of disease on the bone scan, and erythrocyte spermidine and spermine levels with progression. Three patients died of unrelated causes and were excluded from the study, 16 remained in remission with a mean 28 +/- 11 months of followup and 24 had progression (18, or 75%, of whom died of the cancer) with a mean 12 +/- 9 months of followup (p < 0.05 for followup) after initiation of hormonal therapy. Pretreatment performance status, hemoglobin, and erythrocyte spermidine and spermine levels were correlated with progression, hemoglobin and spermine being the most significant independent variables (p = 0.006 and p = 0.001, respectively). Concerning cause-specific survival, only hemoglobin and spermine erythrocyte levels were significant independent variables (p = 0.02 and p = 0.0025, respectively). If confirmed, polyamine erythrocyte levels obtained by a simple blood sample could discriminate at diagnosis patients with a high risk of rapid hormonal relapse who may benefit from a more aggressive primary management.

Aged↗

PubMed1994

Internalization of metformin is necessary for its action on potentiating the insulin-induced Xenopus laevis oocyte maturation.

In this study, metformin (N, N1 dimethylbiguanide) was found to potentiate insulin-induced Xenopus laevis oocyte maturation, a phenomenon of transition from late G2 to M phase of the cell cycle. These cells also accumulated exogenous metformin (130 +/- 6.5 nmol/oocyte). Metformin covalently-coupled to Sepharose 4B beads failed to potentiate the insulin-induced oocyte maturation which suggests that these cells did not take up metformin from the extracellular medium. Addition of metformin alone to Xenopus laevis oocytes did not induce the maturation process, though these cells took up exogenous metformin. Micro-injection of metformin (120 nmol/oocyte) to oocytes accelerated the insulin-induced maturation, but it was lower than in cells which were incubated with free metformin together with insulin. Interestingly, insulin had no effect on metformin uptake by the oocytes. Methylglyoxal-bis(guanylhydrazone), MGBG, an apparent analogue of metformin, induced oocyte maturation. Addition of metformin, either free or Sepharose-bound, did not influence the MGBG-induced 60% maturation of Xenopus laevis oocytes. These results suggest that the internalization of metformin is necessary for its action and its effects are specific on insulin activity.

Animals↗

PubMed1994

[Involvement of polyamines in malignant proliferative processes: antineoplastic effects of a polyamine deficiency].

The fact that tumors require polyamines for growth has been repeatedly demonstrated. In vivo polyamines are available both from endogenous (intracellular biosynthesis) and exogenous sources (food and intestinal microflora). We investigated in rats grafted with Mat-Lylu prostatic adenocarcinoma the distribution between tumor and tissues of orally administered [14C]putrescine (Pt). The amount of radioactivity retained by tumors was directly proportional to the tumor volume. In a tumor of 25 cm3 19% of the totally retained radioactivity was found. The accumulation of Pt by intestinal brush-border membrane vesicles prepared from tumor-bearing animals was significantly higher than by vesicles from healthy rats. Our results indicate that the presence of a tumor induces an adaptive response in the small intestine which stimulates the uptake of exogenous polyamines. Our therapeutic strategy was to realise a total blockade of all endogenous and exogenous sources of polyamines by feeding animals with a drug (DFMO, MDL 72527, antibiotics) containing polyamine deficient chow. We observed that polyamine deprivation largely reduced both primary tumor and metastatic development. Natural Killer cell cytotoxic activity and blood formula were restored to normal values after treatment. Furthermore polyamine deprivation enhanced antitumoral efficacy of chemotherapy.

Animals↗

PubMed1993

Polyamine transport regulation by calcium and calmodulin: role of Ca(2+)-ATPase.

The study was conducted on human leukemia (K 562) cells to characterize the mechanisms implicated in the regulation of the polyamine spermidine (Spd) transport process. The antagonists of calmodulin, trifluoperazine (TFP), W-7 (N-[6-aminohexyl]-5-chloro-1-naphthelenesulfonamide), or mellitin inhibited significantly polyamine Spd uptake in these cells. The translocation of calmodulin towards plasma membrane and a concomitant decrease in its contents in cytosol were directly correlated with the time course increases similar to that of Spd uptake, indicating that calmodulin is recruited towards plasma membrane during the Spd transport process. Diminution of free intracellular calcium, (Ca2+)i, by preincubating the cells in BAPTA (bis[2-amino-5-methylphenoxyl]-ethane-N,N,N',N',-tetraacetate) buffer inhibited Spd transport significantly. Addition of lanthanum (LAN), a molecule known to inhibit Ca2+ efflux via Ca(2+)-ATPase, curtailed Spd uptake by these cells. LAN inhibited Vmax, but not the Km, of Spd uptake, indicating that the former does not directly interact with the polyamine transporter; rather it regulates the transport process, probably via its action on Ca(2+)-ATPase. Calmodulin-stimulated uptake of 45Ca2+ by inside-out vesicles of K 562 cells, a measure of Ca(2+)-ATPase activity. Furthermore, addition of LAN inhibited both basal and calmodulin-stimulated activity of Ca(2+)-ATPase. Thapsigargin (THAP), a molecule known to elevate (Ca2+)i due to its action on the endoplasmic reticulum, increased Spd transport whereas addition of LAN inhibited THAP-stimulated Spd transport activity. THAP increased free (Ca2+)i in these cells, and a pre-addition of LAN to these cells curtailed the THAP-stimulated increases of (Ca2+)i concentrations. Addition of Spd brought about elevations in (Ca2+)i contents. Caffeine also increased (Ca2+)i in these cells; however, it failed to stimulate significantly the Spd uptake process, indicating that (Ca2+)i which is involved in the regulation of polyamine transport pathways does not belong to the calcium-induced calcium-release (CICR) pool. Replacement of Ca2+ from the incubation medium (i.e., 0% Ca2+) resulted in higher uptake activity as compared to that in 100% Ca2+ medium, demonstrating that in 100% Ca2+ medium the calcium efflux process is quickly compensated by calcium refilling/influx from the extracellular medium, while in 0% Ca2+ medium there is perpetual efflux of (Ca2+)i which contributes to higher Spd uptake process. The results of this study suggest that an increase in free (Ca2+)i and its release from the cells via Ca(2+)-ATPase, and concomitant activation of calmodulin, which controls Ca(2+)-pump activity, are involved in the regulation of the Spd uptake process in human leukemia cells.

Biological Transport↗

PubMed1993

The effects of structural analogs of putrescine on proliferation, morphology and karyotype of glioblastoma cells in culture.

In a previous study, we identified regions on the surface of tumor cells which act as acceptor sites for putrescine (Put) and studied the competition between structural analogs of Put (N,N'-tetramethyl-alpha,omega-diaminoalkanes) and Put bound to latex microspheres. A chain of four to seven carbons was necessary for inhibition of Put-latex binding to the cell surface of human glioblastoma (U251) cells. We show here that under the experimental conditions, N,N'-tetramethyl-1,4-butanediamine and N,N'-tetramethyl-1,7-heptanediamine exhibit an antitumor effect. In a first step (1-48 h after treatment), cells exposed to these compounds show large intracellular vacuoles. We failed to detect any acid phosphatase activity in these intracellular structures revealing that they were not lysosomes. Electron microscopy observations argue for the conclusion that these vacuoles are an hypertrophy of the endoplasmic reticulum (ER) and/or of the Golgi vesicles. Our hypothesis is that this typical effect of the analogs reveals that ER could be a physiological target of endogenous polyamines. At a later stage (6 days after treatment), the cells undergo morphological and biochemical changes: thin and long expansions characterize the cells and the GFA protein is overexpressed. Correlated to both these effects, karyotypic modifications are found in chromosomes 3 and 6. These changes evoke a differentiation of the treated cells. The work provides evidence that N-methylated polyamine analogs taking the place of endogenous putrescine demonstrate a hopeful antitumor effect.

Cell Differentiation↗

PubMed1993

Polyamines and prostatic carcinoma: clinical and therapeutic implications.

The erythrocyte polyamines, spermidine and spermine, are known proliferation markers. The authors present their experience with polyamines and prostatic carcinoma. 229 patients with prostatic carcinoma had polyamine erythrocyte determination at diagnosis. Previous results confirmed a tendency to spermidine increase with tumor stage and a significant increase in spermine in metastatic and hormonal escape patients. No correlation was found between polyamine erythrocyte levels and hemoglobin, prostate-specific antigen or tumor grade. 148 prostatic carcinoma patients were followed up. Their pretreatment erythrocyte polyamine levels were correlated to progression. Patients (whatever stage) with rapid progression present significantly enhanced pretreatment erythrocyte spermine levels compared to patients with a favorable outcome. Polyamines are not only proliferation markers but are also necessary for cell division. The authors present their results on polyamine deprivation, combining a polyamine-free diet, polyamine synthesis inhibitors and intestinal tract decontamination, on in vivo tumor growth inhibition of the murine prostatic carcinoma Dunning Mat LyLu tumor model.

Adult↗

PubMed1992

Characterization of metformin transport system in NIH 3T3 cells.

The biochemical properties of the metformin transport system were studied in NIH 3T3 cells. 14C-metformin uptake appeared to be a sodium dependent process. Iso-osmotical replacement of Na+ by choline chloride in the assay medium resulted in a decrease of metformin uptake. Amiloride (200 microM) inhibited the metformin transport by 35% in these cells. Gramicidin, a channel ionophore, was the most effective in inhibiting the metformin transport as compared to valinomycin, a mobile ion carrier, and Ca2+ ionophore (A 23187). Loading of cells with asparagine, ornithine, or polylysine did not influence the uptake process. However, the addition of lysine or arginine significantly stimulated the metformin uptake by NIH 3T3 cells. Similarly, the addition of metformin stimulated the arginine uptake by these cells, suggesting that metformin shares the y+ transport system. Metformin inhibited competitively the uptake of 14C-spermidine, a molecule of the polyamine family, by NIH 3T3 cells, whereas the latter failed to influence the uptake of the former significantly by these cells. Incubation of NIH 3T3 cells in the presence of difluoromethyl-ornithine (a suicidal inhibitor of polyamine biosynthesis) stimulated the spermidine, but not the metformin, uptake by these cells. Interestingly, a prolonged incubation of these cells in the presence of metformin failed to down-regulate the spermidine transport process. The spermidine- and methylglyoxal-bis(guanylhydrazone), MGBG-transport deficient (3T3MG) cells which do not accumulate exogeneous spermidine or MGBG, took up 14C-metformin. However, 14C-metformin uptake by 3T3MG cells was lower than that by normal NIH 3T3 cells.

3T3 Cells↗

PubMed1992

Phorbol esters augment polyamine transport by influencing Na(+)-K+ pump in murine leukemia cells.

In this report, we elucidate the role of Na(+)-K+ pump in the regulation of polyamine spermidine (Spd) transport in murine leukemia (L 1210) cells in culture. Ouabain, known to bind extracellularly to the alpha-subunit of the Na(+)-K+ pump, inhibits the pump activity. The L 1210 cells were found to possess ouabain binding sites at 7.5 fmol/10(6) cells. Ouabain significantly inhibited the Spd uptake in a dose-dependent manner. The maximum inhibition of Spd uptake by ouabain was observed beyond 200 microM. Spd transport was inversely correlated with the [3H]ouabain binding to L 1210 cells: an increase in the saturation of ouabain binding to L 1210 cells resulted in a decrease of the Spd uptake process. Treatment of L 1210 cells with protein kinase C activator phorbol esters increased the Spd transport and, also, ouabain-sensitive 86Rb+ uptake, a measure of the activity of the Na(+)-K+ pump. H-7, a protein kinase C inhibitor, significantly inhibited the ouabain-sensitive 86Rb+ uptake by L 1210 cells. Phorbol esters stimulated the level, but not the rate, of 22Na+ influx. Addition of H-7 to L 1210 cells inhibited the 22Na+ influx process. A concomitant phorbol ester-induced increase in 22Na+ influx, [14C]Spd uptake, together with the functioning of Na(+)-K+ pump, indicates the role of the "Na+ cycle" in the regulation of the polyamine transport process.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1992

Depletion in nuclear spermine during human spermatogenesis, a natural process of cell differentiation.

Polyamines (PA), polycations present in all mammalian cells, are essential for cell proliferation and differentiation. In vitro, PA are known to bind to DNA with a high affinity. In vivo, the intimate association of endogenous PA with highly condensed chromatin has been reported. During spermatogenesis, when processes of cell proliferation and differentiation take place, the potential role of polyamines has not been studied in depth. We report here the PA levels measured in human spermatogenic cell nuclei at different stages of differentiation. Cell populations (spermatocytes and round, elongating, or elongated spermatids) were obtained after submitting human testes to a trypsin-deoxyribonuclease digestion, then to a centrifugal elutriation and Percoll gradient centrifugation. A significant and progressive nuclear spermine level decrease was observed from primary spermatocytes to elongated spermatids. This release of spermine from nuclei was concomitant with three major events in mammalian spermiogenesis: the reduction of DNA transcription activity, the replacement of histone proteins by protamines, and the compaction of chromatin. This is the first report arguing a release of nuclear spermine during an in vivo physiological cell differentiation process.

Cell Differentiation↗

PubMed1992

[The diagnostic value of erythrocyte polyamines (EPA) in prostatic adenocarcinoma (PA): apropos of 100 patients].

Spermidine and spermine are ubiquitous polyamines which are intensely metabolised in the prostate. Polyamines are involved in the processes of proliferation and differentiation of normal and neoplastic cells. As the erythrocyte levels of these polyamines are correlated with the intratumoral levels, we assayed EPA in 45 controls, 66 patients with benign prostatic hypertrophy and 100 patients with prostatic cancer. Erythrocytic polyamines are markers of proliferation and prostatic metastases and can be used to distinguish between hormone-sensitive and hormone-resistant patients. Although non-specific, polyamines constitute circulating markers of the state of tumour proliferation of a given patient and definitely have a prognostic value which needs to be evaluated by further studies.

Adenocarcinoma↗

PubMed1991

Exogeneous diacylglycerols downregulate the activity of Na(+)-K+ pump in Xenopus laevis oocytes.

In this study, cell permeable diacylglycerols, sn-1,2-dioctanoglycerol (DiC8), and sn-1-oleoyl-2-acetylglycerol (OAG) were found to downregulate the activity of Na(+)-K+ pump in Xenopus laevis oocytes. Both DiC8 and OAG decreased the binding of [3H]ouabain to intact oocytes while phorbol esters did not appreciably influence the same. These diacylglycerols inhibited the amiloride-sensitive 22Na+ influx and ouabain-sensitive 86Rb+ uptake in the oocytes. Furthermore, DiC8 prevented the 22Na+ efflux from the oocytes preloaded with 22Na+. Addition of H-7 to DiC8- and OAG-treated oocytes stimulated the pump activity curtailed by the two latters. The impairment of Na(+)-K+ pump activity by diacylglycerols suggests that protein kinase C activators may stimulate endocytosis of membrane-coupled Na(+)-K+ ATPase.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗