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P Lebrun

Publications and source records attributed to P Lebrun.

At least 19 recordsLinked to original sources
PubMed1995

Simultaneous measurement of 45Ca outflow and human placental lactogen release from placental explants.

Kinetics of 45Ca outflow and human placental lactogen (hPL) release were characterized in human placental explants. Measurements of the rate of 45Ca and [3H]-sucrose (extracellular space marker) outflow from preloaded explants showed that, after a 40 min washout period, the 45Ca effluent radioactivity presumably originated from an intracellular compartment. This view was further supported by the La3+ and temperature sensitivity of the 45Ca outflow. Moreover, the addition of ionomycin as well as an increase in the extracellular Ca2+ or Ba2+ concentration provoked a dose-dependent rise in both the 45Ca outflow and hPL release. There were no systematic temporal analogies between the pattern of 45Ca outflow and hPL release. Taken together, these observations suggest that the stimulation of 45Ca outflow reflects an increased rate of 40Ca entry. The present data also extend previous observations indicating that hPL release can be stimulated by Ca2+ entry. Lastly, the 'in vitro' method described herein allows one to compare rapid changes in hPL release with associated ionic events and can be used to further document the relationships between placental secretory responses and cell calcium metabolism.

Barium↗
PubMed1994

Cationic and secretory effects of BPDZ 44 and diazoxide in rat pancreatic islets.

The present study aimed at comparing the effects of low concentrations of BPDZ 44, a new pyridothiadiazine derivative, and diazoxide on 86Rb outflow, 45Ca outflow, 45Ca uptake and insulin release from rat pancreatic islets. Both drugs caused similar modifications, but the effects of BPDZ 44 on the cationic and secretory events were much more marked than those of diazoxide. It is suggested that BPDZ 44 could be valuable tool for further studies of the KATP channels.

Animals↗
PubMed1994

Ca2+ entry through L-type voltage-sensitive Ca2+ channels stimulates the release of human chorionic gonadotrophin and placental lactogen by placental explants.

The release of human chorionic gonadotrophin (hCG) and placental lactogen (hPL) by human placental explants can be stimulated by Ca2+ entry. The aim of the present study was to characterize the modality of Ca2+ entry in the presence of high extracellular K+ concentration ([K+]o). A rise in [K+]o from 5 to > or = 50 mM induced a rapid and marked increase in the release of hCG and hPL from human term placental explants. The stimulatory effects of an excess [K+]o on the release of hCG and hPL were blocked in the absence of extracellular Ca2+ or in the presence of 0.5 mM Co2+. The presence of 50 microM methoxyverapamil, 20 microM nifedipine or 40 microM Cd2+ in the medium inhibited the stimulatory effects of [K+]o addition. Lastly, 40 microM Ni2+ failed to affect the increases in hCG and hPL releases elicited by [K+]o addition. Our data clearly show that a rise in [K+]o stimulates the release of hCG and hPL from placental explants. These secretory effects can be viewed as resulting from a Ca2+ entry through voltage-sensitive Ca2+ channels of the L-type.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1994

Inhibition of Na/Ca exchange by Phe-Met-Arg-Phe-NH2 (FMRFa)-related peptides in intact rat pancreatic B-cells.

Phe-Met-Arg-Phe-NH2 (FMRFa)-related peptides were recently shown to inhibit Na/Ca exchange in cardiac sarcolemmal vesicles. In the present study, we examined the effects of FMRFa-related peptides on Na/Ca exchange in intact (pancreatic B) cells. At 2.8 mM glucose, FMRFa-related peptides only weakly inhibited Na/Ca exchange although their effect was more marked under depolarizing conditions. The peptides blocked neither the Na/K-ATPase nor Ca2+ channels but slightly reduced membrane K+ permeability. Our data indicate that FMRFa-related peptides are weak and non-specific inhibitors of Na/Ca exchange in intact B cells. The data do not confirm the view that the peptides may exert some of their physiological modulatory role by inhibiting Na/Ca exchange.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1994

The release of human chorionic gonadotrophin and placental lactogen by placental explants can be stimulated by Ca2+ entry through a Na(+)-Ca2+ exchange process.

Isosmotical replacement of extracellular Na+ ([Na+]o) by K+, choline and to a lesser extent by saccharose stimulated the release of chorionic gonadotrophin and placental lactogen from human term placental explants. The effect of [Na+]o removal on the release of both hormones was concentration-dependent and was inhibited in the absence of extracellular Ca2+ or in the presence of 0.5 mM Co2+, a Ca2+ entry blocker. Blockers of the voltage-sensitive Ca2+ channels (20 microM nifedipine and 50 microM methoxyverapamil) or Na+ channels (5 microM tetrodotoxin) did not affect the stimulatory effects of [Na+]o omission. By contrast, Mg2+ and Sr2+ (10 mM) as well as amiloride (2 mM) and its analogue 2',4'-dimethylbenzamil (50 microns), all known to affect the Na(+)-Ca2+ exchange, markedly reduced the increase in hormone release elicited by [Na+]o removal. Lastly, the secretory responses to [Na+]o deprivation were increased in the presence of 2 mM ouabain, an inhibitor of the Na(+)-K+ ATPase. These results indicate for the first time that [Na+]o omission provokes a Ca(2+)-dependent stimulation of human chorionic gonadotrophin and placental lactogen releases. The pharmacological dissection of the secretory effects of [Na+]o removal supports the existence of a process of Na(+)-Ca2+ exchange in placental cells.

Calcium↗
PubMed1994

Inhibition of Na/Ca exchange stimulates insulin release from isolated rat pancreatic islets.

Na/Ca exchange was recently shown to regulate cytosolic free Ca2+ concentration ([Ca2+]i) in the pancreatic B-cell. The aim of the present study was to provide direct evidence that inhibition of the activity of the exchange may also increase insulin release. In the presence of extracellular Na+, caffeine stimulated 45Ca outflow but did not increase insulin release from islets perifused in the presence of 2.8 mM glucose. By contrast, in the absence of extracellular Na+, caffeine almost failed to increase 45Ca outflow and reversibly stimulated insulin release despite the fact that the absence of extracellular Na+ per se reduced basal insulin release. Similar findings were observed in islets perifused at a higher glucose concentration (8.3 mM) except that, in the presence of extracellular Na+, caffeine more markedly increased 45Ca outflow and stimulated insulin release. Our data provide direct evidence that inhibition of Na/Ca exchange with resulting blockade of Ca2+ outflow may increase insulin release from the pancreatic B-cell under suitable experimental conditions.

Animals↗
PubMed1994

Injections of complexes made of dsDNA and specific polyclonal antibodies extend MRL lpr mouse survival: a pilot study.

Antibodies towards double-strain (ds) DNA are responsible for the development of lupus nephritis both in human and animal models. A method by which one would suppress the production of pathogenic idiotypes could therefore prevent the development of nephritis. To this end, we prepared polyclonal anti-dsDNA antibodies by immunoaffinity from a serum pool of MRL/MpJ-lpr mice, a strain that develops an early form of nephritis identical to its human counterpart. Antigen-antibody complexes were prepared by addition of dsDNA. Such complexes have the potential of altering the anti-DNA antibody response and boosting the production of specific anti-idiotypic antibodies. Two groups of 14 MRL lpr mice were treated by regular intraperitoneal injections of 10 micrograms dsDNA-anti-dsDNA complexes or carrier buffer, starting at the age of 4 weeks, namely, prior to the appearance of nephritogenic anti-dsDNA IgG antibodies. We show here that such a treatment significantly extended the survival of treated mice compared with the control group. Five treated mice were still alive at month 11 compared with two in the control group. In addition, microscopic kidney examination at the time of death showed less lesions in the treated group compared with controls. This study indicates that complexes made of dsDNA and anti-dsDNA can delay the development of nephritis in the MRL lpr mouse strain.

Animals↗
PubMed1992

Mechanical and ionic response of rat aorta to diazoxide.

Diazoxide provoked concentration-dependent and endothelium-independent relaxations of the mechanical responses evoked by low concentrations of KCl. Glibenclamide, tolbutamide and tetraethylammonium shifted the concentration-response curve for diazoxide to the right. The drug also caused a dose-dependent stimulation of 86Rb outflow which was inhibited by glibenclamide and tolbutamide. Diazoxide (10(-4) and 10(-3) M) inhibited the contractions elicited by 10(-1) M K+ and provoked a concentration-dependent reduction in the contractile responses to Ca2+. Diazoxide also reduced the KCl (8 x 10(-2) M)-induced increase in 45Ca outflow. These data indicate that the vasorelaxant properties of diazoxide are probably related to an inhibition of Ca2+ entry into smooth muscle cells. The reduction in Ca2+ entry appears to result from K+ channel activation. At high concentrations, diazoxide also exhibited antagonistic actions on voltage-sensitive Ca2+ channels.

Animals↗
PubMed1992

K+ channel openers and insulin release.

Recent in vivo and in vitro experiments suggested that the smooth muscle relaxation mediated by diverse pharmacologic agents resulted from K+ channel opening. Pinacidil, cromakalim, nicorandil, RP 49356, minoxidil sulfate and diazoxide belong to this new group of smooth muscle relaxants: the "K+ channel openers". Because modifications in the K+ permeability are known to represent a critical event in the insulin-releasing process, numerous studies have been performed in order to examine the putative effects of K+ channel openers on B-cell function. The aim of the present review is to summarize these experimental data which are sometimes divergent.

Animals↗
PubMed1992

Cationic and secretory effects of glimepiride and glibenclamide in perifused rat islets.

The effects of glimepiride and glibenclamide upon 86Rb outflow, 45Ca outflow and insulin release were examined in rat islets perifused at low (zero to 2.8 mM) or close-to-normal (8.3 mM) D-glucose concentrations. At the low hexose concentrations, a marked and not reversible decrease in 86Rb outflow contrasted with a rapid and reversible increase in 45Ca outflow. The latter increase was abolished in the absence of extracellular Ca2+, and was not associated with any pronounced stimulation of insulin release. Inversely, in the presence of 8.3 mM D-glucose, a comparable increase in 45Ca efflux now coincided with an increase in 86Rb efflux and a marked and not reversible stimulation of insulin release. Whether in terms of the time course or glucose dependency of the cationic and secretory responses, a coupled increase in both 40Ca inflow and 45Ca outflow thus coincided with either negative or positive changes in 86Rb outflow and either minimal or marked changes in insulin output. Such dissociated behaviours suggest that the insulinotropic action of hypoglycemic sulfonylureas is not necessarily attributable solely to a primary decrease in K+ conductance.

Animals↗
PubMed1992

Anoxia and glucose-sensitive 86Rb outflow from rat portal vein.

Exposure of rat portal veins to an N2-gassed buffer markedly increased 86Rb outflow. Moreover, glucose caused a pronounced reduction in 86Rb outflow from portal veins perfused with an N2-gassed buffer. Pinacidil, cromakalim and diazoxide provoked a sustained increase in 86Rb outflow. The stimulatory effect of pinacidil was not impaired in the absence of extracellular Ca2+ but was completely abolished by glibenclamide. These observations are compatible with the involvement of a metabolic process in the control of the K+ permeability, namely with the existence in rat portal veins of ATP-sensitive K+ channels.

Adenosine Triphosphate↗
PubMed1992

[Treatment of hypertension in diabetes: threshold of intervention and therapeutic options].

Early screening for hypertension in diabetic patients and for glycoregulation abnormalities in hypertensives is justified by the additive cardiovascular risks when hypertension and diabetes co-exist and by the accelerated development of diabetic nephropathy and retinopathy if hypertension co-exists. In insulin-dependent diabetes, hypertension is generally preceded by microalbuminuria, known to be reduced by angiotensin converting enzyme inhibitors. The requirement for nephropathy prevention and the hemodynamic and/or tissular effects of this therapeutic class could justify their use at a blood pressure level less than that conventionally considered hypertensive. This strategy must be confirmed by prospective trials, already underway, evaluating the nephroprotective efficacy of this therapy. In non-insulin-dependent diabetes, hypertension is often present before the diabetes is diagnosed and antihypertensive therapy, especially thiazide diuretics, could play a demasking or favorizing role. The optimal blood pressure level to which these patients at high renal and coronary risk should be lowered still has to be determined. A prospective study, comparing the effects of strict (treated diastolic blood pressure less than 80 mmHg) and less strict (treated diastolic blood pressure between 90 and 100 mmHg) hypertensive control on coronary event prevention in essential hypertension, is in progress and will have important implications for hypertension treatment in diabetics. Appropriate treatment of other risk factors, such as hyperlipidaemia and smoking, contributes to coronary and renal prevention in all diabetic hypertensives.

Albuminuria↗
PubMed1991

RP 49356: inhibitory effects of ionic and secretory events in rat pancreatic islets.

Rp 49356, a 'K+ channel opener', inhibited 86Rb outflow, 45Ca outflow and insulin release from glucose-stimulated islets perifused in the presence of Ca2+. The drug lost its capacity to reduce 86Rb outflow in islets exposed to glucose-free or Ca(2+)-free medium. These observations suggest that RP 49356 might exhibit antagonistic actions on B-cell Ca2+ channels. This will, in turn, reduce glucose-stimulated insulin output and Ca(2+)-dependent 86Rb outflow.

Animals↗
PubMed1991

Ionic and secretory response of pancreatic islet cells to minoxidil sulfate.

Minoxidil sulfate is an antihypertensive agent belonging to the new class of vasodilators, the "K+ channel openers." The present study was undertaken to characterize the effects of minoxidil sulfate on ionic and secretory events in rat pancreatic islets. The drug unexpectedly provoked a concentration-dependent decrease in 86Rb outflow. This inhibitory effect was reduced in a concentration-dependent manner by glucose and tolbutamide. Minoxidil sulfate did not affect 45Ca outflow from islets perfused in the presence of extracellular Ca++ and absence or presence of glucose. However, in islets exposed to a medium deprived of extracellular Ca++, the drug provoked a rise in 45Ca outflow. Whether in the absence or presence of extracellular Ca++, minoxidil sulfate increased the cytosolic free Ca++ concentration of islet cells. Lastly, minoxidil sulfate increased the release of insulin from glucose-stimulated pancreatic islets. These results suggest that minoxidil sulfate reduces the activity of the ATP-sensitive K+ channels and promotes an intracellular translocation of Ca++. The latter change might account for the effect of the drug on the insulin-releasing process. However, the secretory response to minoxidil sulfate could also be mediated, at least in part, by a modest Ca++ entry.

Animals↗
PubMed1991

Inhibition of Na/Ca exchange in pancreatic islet cells by 3',4'-dichlorobenzamil.

Na/Ca exchange may play a role in Ca2+ extrusion from the pancreatic B cell. The role played by the exchanger was examined by characterizing the effects of 3'-4'-dichlorobenzamil on ionic fluxes and insulin release in normal rat pancreatic islet cells. 3',4'-Dichlorobenzamil potently inhibited 45Ca uptake mediated by reverse Na/Ca exchange (IC50: 18 microM) in islet cells. The drug failed to decrease intracellular pH but reduced 86Rb outflow from perifused islets. The effects of glucose and 3',4'-dichlorobenzamil on 86Rb outflow were not additive. The drug potently blocked 45Ca uptake through voltage-sensitive Ca2+ channels (IC50: 7.5 microM). In the presence of extracellular Ca2+ and 3',4'-dichlorobenzamil, glucose lost part of its ability to reduce 45Ca outflow. The drug failed to affect the secondary rise in 45Ca outflow induced by the sugar. In the absence of extracellular Ca2+, 3',4'-dichlorobenzamil induced a delayed inhibition of 45Ca outflow, the effect of the sugar and the drug being not additive. This effect of 3',4'-dichlorobenzamil and its ability to impair the inhibitory effect of glucose were reproduced by the removal of extracellular Na+ and disappeared under the latter experimental condition. 3',4'-Dichlorobenzamil did not affect insulin release in the absence of glucose but significantly increased glucose-induced insulin release when used at a high concentration. It is concluded that 3',4'-dichlorobenzamil is a potent inhibitor of the process of Na/Ca exchange in the pancreatic B cell. Unfortunately, the drug is of poor specificity and blocks, in the same range of concentrations, both K+ channels and voltage-sensitive Ca2+ channels. The data also indicate that glucose inhibits 45Ca outflow from pancreatic islets to a great extent (at least 75%) by inhibiting Na/Ca exchange. The type of Na/Ca exchange that is inhibited by glucose, remains to be elucidated.

Amiloride↗