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Y Giudicelli

Publications and source records attributed to Y Giudicelli.

At least 73 records · Page 4Linked to original sources
PubMed1989

Role of adenosine 3',5'-monophosphate and the Ri-receptor Gi-coupled adenylate cyclase inhibitory pathway in the mechanism whereby adrenalectomy increases the adenosine antilipolytic effect in rat fat cells.

The aim of this study was to establish the mechanism by which adrenalectomy promotes the antilipolytic effect of the adenosine analog (-)-N6-(R-phenyl-isopropyl)adenosine (R-PIA) in rat fat cells. This action of adrenalectomy was not specific for R-PIA, since it was also observed with nicotinic acid and was prevented by phosphodiesterase inhibitors. In contrast, the inhibitory effect of R-PIA and nicotinic acid toward isoproterenol-stimulated cAMP accumulation was unaltered by adrenalectomy regardless of whether phosphodiesterase inhibitors were present. Whatever the conditions used, however, the cAMP levels in adrenalectomized rat adipocytes were one quarter to one third of those in sham-operated rats and remained below the limit over which variations in cAMP had no more influence in lipolysis. Both total and particulate low Km cAMP phosphodiesterase activities per adipocyte were decreased in adrenalectomized rats, but the stimulatory responses of the particulate enzyme to R-PIA remained unchanged. Pertussis toxin-catalyzed ADP ribosylation studies revealed a marked decrease in the total amount of the alpha-subunits of Go and the adenylate cyclase inhibitory regulatory protein Gi after adrenalectomy. However, the inhibitory dose-response curves of adenylate cyclase to R-PIA, nicotinic acid, GTP, guanylylimidodiphosphate, and guanosine 5'-O-(3-thiotriphosphate) were unaltered by adrenalectomy, indicating that the inhibitory function of Gi is unimpaired by adrenalectomy. Lastly, adrenalectomy resulted in a 60% reduction of the Mn2+-stimulated adenylate cyclase activity/adipocyte, which indicates that adrenalectomy causes a defect in adenylate cyclase catalytic activity. Thus, enhanced antilipolytic effects of R-PIA induced by adrenalectomy do not involve increased function of the adenosine receptor Gi-coupled adenylate cyclase inhibitory pathway, but are related to abnormally low intracellular cAMP levels due to defective adenylate cyclase catalytic activity.

1-Methyl-3-isobutylxanthine↗
PubMed1989

Studies on the mechanism of the decreased guanine nucleotide stimulatory effects on adenylate cyclase after adrenalectomy in rat adipocytes.

In adipocyte membranes from adrenalectomized rats: (i) the defect in the stimulatory effects of guanine nucleotides on adenylate cyclase is greater with GTP than with GppNHp and appears to concern the GS-C complex and not the HR-GS-C ternary complex; (ii) the GTP-ase activity is enhanced; (iii) maximal alpha S-C interaction (tested by the responses to forskolin, cholera toxin or NaF) is unaltered and (iv) the alpha S affinity for guanine nucleotides and the GDP/GppNHp exchange reaction are both unimpaired. These data suggest that the enhanced GTP-ase activity together with a decrease in the catalytic activity of the alpha S-GTP-C complex are the likely mechanisms whereby adrenalectomy causes a defect in the fat cell adenylate cyclase response to guanine nucleotides.

Adenylyl Cyclases↗
PubMed1988

Increased adenylate cyclase catalytic activity explains how estrogens "in vivo" promote lipolytic activity in rat white fat cells.

Estradiol administration (5 micrograms per day x 4 days) to ovariectomized rats resulted in a 60-70% increase in the maximal lipolytic response of their white adipocytes to isoproterenol, epinephrine, IBMX and forskolin. These altered lipolytic responses were accompanied by parallel changes in the intracellular cyclic AMP levels found in response to 1 mM IBMX alone (+ 106%) or combined with submaximal concentrations of isoproterenol (+205%), epinephrine (+190%) and forskolin (235%). Studies of the adenylate cyclase activity revealed an overall increase in the stimulatory responsiveness of the enzyme (+150 to +200%) after the estradiol-treatment, regardless of the stimulatory agents tested (GTP, GppNHp, fluoride, isoproterenol, ACTH, forskolin). Finally, the finding of a 2-fold enhancement of the Mn2+ (+/- GDP beta S)-stimulated adenylate cyclase activity after the estradiol-treatment strongly suggests that increased activity of the catalytic subunit of this enzyme is the likely mechanism whereby estrogens promote lipolysis in rat fat cells.

1-Methyl-3-isobutylxanthine↗
PubMed1988

Permissive action of glucocorticoids on catecholamine-induced lipolysis: direct "in vitro" effects on the fat cell beta-adrenoreceptor-coupled-adenylate cyclase system.

Exposure of adipose tissue fragments to dexamethasone leads to enhanced lipolytic and cyclic AMP responses of isolated fat cells to isoproterenol. This permissive effect of the steroid is dose-dependent, prevented by the glucocorticoid receptor antagonist RU 38486, maximum after 48 h exposure to 10 nM dexamethasone and affects only the amplitude of the maximal response (+50%). Exposure to dexamethasone also induces an increase in both the number of beta-adrenergic receptors (+30%), and the adenylate cyclase-catalytic activity (+64%) and - responses to GTP (+114%) and isoproterenol (+55%). These data strongly suggest that the permissive effect of glucocorticoids towards lipolysis "in vivo" results at least in part from a glucocorticoid-receptor mediated action of these hormones on the fat cell membranous components involved in the beta-adrenergic control of lipolysis.

Adenylyl Cyclases↗
PubMed1988

Influence of androgenic status on the alpha 2/beta-adrenergic control of lipolysis in white fat cells: predominant alpha 2-antilipolytic response in testosterone-treated-castrated hamsters.

The aim of this study was to evaluate the influence of castration with or without testosterone propionate (TP) administration (one daily injection of 1 mg for 10 days) on the fat cell lipolytic activity in male hamsters. Basal and maximal lipolytic responses to the pure beta-adrenergic agonist isoproterenol, the mixed alpha 2-and beta-adrenergic agonist epinephrine, and the nonadrenergic compounds ACTH and 3-isobutyl-1-methylxanthine were all reduced by half in castrated animals. TP treatment restored these defective responses to control values, except the response to epinephrine which remained paradoxically unchanged. Sensitivity of lipolysis to epinephrine was unimpaired by castration but markedly reduced (10-fold) in TP-treated castrated hamsters. The antilipolytic potencies of the alpha 2-component of epinephrine and of the two alpha 2-agonists, UK 14304 and clonidine, were reduced by half in castrated animals, and returned to a value slightly higher than control after TP treatment. These changes in lipolysis were accompanied by parallel alterations in the stimulated cAMP responses to isoproterenol and forskolin but not to epinephrine. The latter was either unimpaired by castration or was clearly inhibited after TP treatment. Castration also induced a 2-fold decrease in the inhibitory potency of clonidine toward forskolin-stimulated cAMP production. Finally, these changes in the potency of clonidine were accompanied by parallel variations of the number of fat cell alpha 2-adrenoreceptors. These results indicate that testosterone in vivo, while increasing the beta-adrenergic lipolytic action of catecholamines (possibly through enhancement of the adenylate cyclase activity), promotes, to a greater extent, their alpha 2-adrenoreceptor-mediated antilipolytic potency. By providing the first demonstration that the androgenic status controls the functional alpha 2/beta-adrenergic balance in fat cells, this study also emphasizes the potential importance of such a control in the mechanisms underlying the sex-related differences in adipose tissue regional distribution and fat cell size.

1-Methyl-3-isobutylxanthine↗
PubMed1987

Ethanol alters the adenosine receptor-Ni-mediated adenylate cyclase inhibitory response in rat brain cortex in vitro.

It has been suggested that ethanol stimulates adenylate cyclase in vitro through an increased function of Ns, the activatory component of adenylate cyclase. Because of the interaction of Ns with Ni, the adenylate cyclase inhibitory component, we have studied the effect of ethanol (0.05-0.2 M) on Ni-mediated adenylate cyclase inhibition caused by the adenosine analog N6-phenylisopropyladenosine (N6-PIA) in brain cortical membranes. Ethanol did not alter N6-PIA binding to the adenosine Ri-receptors, stimulated slightly basal adenylate cyclase activity but abolished adenylate cyclase inhibition due to N6-PIA, suggesting an effect of ethanol on the inhibitory coupling pathway. This was further supported by loss of the adenylate cyclase inhibitory response to GTP (greater than 10(-5) M). It thus seems that, besides its effect on the Ns system, ethanol may also impair Ni-mediated adenylate cyclase responses in rat cerebral cortex.

Adenosine↗
PubMed1987

Evidence that the lipolytic defect induced by estradiol-treatment in hamster adipocytes is related to an estrogen receptor-mediated defect in the adenylate cyclase catalytic subunit but not in Ns.

This study demonstrates that estradiol-treatment (10 micrograms per day x 5 days) does not impair the level of Ns, the adenylate cyclase stimulatory regulatory protein, in hamster fat cell membranes. In addition, this report shows that the defective cyclic AMP response induced in intact adipocytes by the estradiol-treatment is either unaltered by the administration of alpha-bromocriptine or abolished by tamoxifen- or 4-hydroxytamoxifen-treatment. It can thus be concluded that the reduced lipolytic response found in hamster fat cells after estradiol-treatment is related only to an estradiol-receptor-mediated defect in adenylate cyclase catalytic subunit activity which is independent from increased prolactin secretion.

Adenylyl Cyclases↗
PubMed1986

Fasting increases fat cell adenylate cyclase sensitivity to stimulatory agonists through enhanced ability of the stimulatory regulatory component Ns to dissociate.

In rat fat cell membranes, a 72-hour fasting fails to alter the adenylate cyclase stimulatory responses to Mn2+, forskolin and cholera toxin and the cholera toxin catalyzed [alpha-32P] ADP ribose incorporation into the Mr = 42,000 and 46,000/48,000 alpha s peptides of Ns. In contrast, dose-response curves for GTP-stimulation of basal and isoproterenol-stimulated adenylate cyclase display higher maximal responses in fasted rats under conditions restraining (2 mM Mg2+) but not promoting (10 mM Mg2+) the dissociation of Ns. Moreover, at 10 mM Mg2+, the sensitivity of isoproterenol-stimulated adenylate cyclase to GTP is clearly increased in fasted rats. Finally, fasting reduces by 40% the lag-phase of adenylate cyclase activation by Gpp(NH)p. Taken together, these results are consistent with the hypothesis that the permissive effect of fasting on the fat cell adenylate cyclase response to stimulatory agonists is related to increased ability of Ns and the ternary H.R.Ns. complex to dissociate which is likely due to enhanced Ns affinity for guanine nucleotides.

Adenylyl Cyclases↗
PubMed1986

Increased sensitivity of fat cell adenylate cyclase to stimulatory agonists during fasting is not related to impaired inhibitory coupling system.

In rat adipocytes, inhibition of the forskolin-stimulated cyclic AMP response by nicotinic acid and N6-phenylisopropyladenosine was unaltered by a 72 h fasting. Under assay conditions favouring inhibition, basal and forskolin-stimulated adenylate cyclase responses to inhibition by GTP and nicotinic acid were also unimpaired by fasting. Under the same conditions, however, low GTP concentrations elicited a clear activatory effect in membranes from fasted but not from fed rats. Fasting failed to alter the incorporation of [32P]ADP ribose into the alpha i-subunit of Ni and the attenuation of nicotinic acid inhibitory action that are both induced by pertussis toxin. These results, demonstrating unimpaired inhibitory control of adenylate cyclase in starved rat adipocytes, suggest that the permissive effect of fasting on the action of stimulatory receptor agonists in fat cells reflects a specific increase in the activity of the adenylate cyclase stimulatory coupling system.

Adenylate Cyclase Toxin↗
PubMed1986

Are the metabolic characteristics of congenital intraspinal lipoma cells identical to, or different from normal adipocytes?

Congenital intraspinal lipomas are frequently responsible for progressive neurological deficits caused by distortion or compression of the nervous system. Since fat metabolism in these lesions has not been previously studied, the aim of this study was to determine whether intraspinal lipoma cells behave like lipomas or like normal adipocytes. In 11 patients, intraspinal lipoma cells were compared with normal adipocytes isolated from adjacent subcutaneous adipose tissue for the following parameters: lipoprotein lipase (LPL), lipogenesis from U14C glucose, beta-receptor number, adenylate cyclase activity, cyclic AMP production, and lipolysis in response to beta- and alpha 2-adrenergic agonists. No significant difference between these two cell populations was found, suggesting that intraspinal lipomas are not lipomatous tumors, but hamartomatous lesions capable of growth and regression along with the changes in the rest of the fatty pool. This emphasizes the danger of an abnormal weight gain, as well as the possible usefulness of an hypocaloric diet in patients who worsen in spite of previous surgery.

Adipose Tissue↗
PubMed1986

Estradiol treatment decreases the lipolytic responses of hamster white adipocytes through a reduction in the activity of the adenylate cyclase catalytic subunit.

After 5 days of daily administration of 10 micrograms estradiol to 6-week-old male hamsters, the in vitro maximal lipolytic and cAMP responses of white adipocytes to isoproterenol, epinephrine, ACTH, and theophylline were reduced by one half, with no change in the sensitivity of these responses. In contrast, the antilipolytic response to the alpha 2-adrenergic agonist clonidine was unimpaired. beta-Adrenergic receptor number and affinity, assessed in intact cells with [3H]CGP-12177 binding, showed no difference between control and estradiol-treated hamsters. In adipocyte membranes from estradiol-treated hamsters, maximal adenylate cyclase responses to Mn2+, GTP alone or in combination with isoproterenol, ACTH, or fluoride were all decreased by 30-40% below the values found in controls, but the sensitivity of these responses was unaltered. The maximum velocity (Vmax) of adenylate cyclase was reduced by one half in estrogen-treated animals, but the Michaelis-Menten constant (Km) of the enzyme for ATP was unchanged. Finally, complementation of adipocyte membranes with solubilized human erythrocyte Ns failed to restore to control values the maximal adenylate cyclase response to isoproterenol plus guanosine 5'-[beta, gamma-imido]-triphosphate in the estradiol-treated hamsters. These results indicate that a defect in the catalytic subunit of adenylate cyclase is one of the mechanisms through which estradiol treatment reduces the lipolytic response of hamster white adipocytes.

Adenylyl Cyclase Inhibitors↗
PubMed1986

Intraspinal lipomas with spina bifida. Prognosis and treatment in 73 cases.

The authors present a series of 73 cases of intraspinal lipomas in the lumbosacral region. Sixty-four patients were operated on, 43 of these under intraoperative monitoring of neural function. The results of this series and of major series published in the past 10 years demonstrate both the potential severity of these lesions (which are responsible for progressive neurological deficits in 56% of affected cases) and the benignity of their surgical treatment. The authors emphasize the usefulness of systematic early surgical treatment of these lesions.

Adolescent↗
PubMed1986

A reliable assay for beta-adrenoceptors in intact isolated human fat cells with a hydrophilic radioligand, [3H]CGP-12177.

The beta-adrenergic receptors of isolated human fat cells were identified using a new hydrophilic beta-adrenergic radioligand (+/-)[3H]CGP-12177. The results were compared with those from [3H]dihydroalprenolol binding to fat cells and membranes. [3H]CGP-12177 binding to isolated fat cells showed lower nonspecific binding (less than 15% of total binding) than the lipophilic [3H]dihydroalprenolol (40-60%) at 3 times the KD. At 37 degrees C, [3H]CGP-12177 binding was rapid, reversible, of high affinity (1.2 +/- 0.3 nM) and saturable. The total number of binding sites per cell in subcutaneous adipocytes was 25,000 +/- 6,000 and was equivalent to that found using membrane fractions. Displacement of [3H]CGP-12177 bound to adipocytes by propranolol was stereoselective, consistent with competition at a single site, and had the same characteristics as in membranes. The displacement curves of the beta 1-selective antagonists (atenolol and betaxolol) were biphasic, the high affinity displacement accounting for 70% of the total binding sites. Beta-adrenergic agonists also competed with [3H]CGP-12177 binding in the order of potency: (-) isoproterenol greater than (-) norepinephrine greater than (-) epinephrine, similar to that found in membranes and in in vitro studies on the lipolytic activity of isolated fat cells. This study demonstrates that the sites specifically labeled by [3H]CGP-12177 are the physiological beta-adrenoceptors and also shows that the ligand is better than [3H]dihydroalprenolol for the accurate identification of these receptors in intact human adipocytes. The methodology, which requires biopsies of less than 1 gram of adipose tissue, can be of potential interest for clinical studies investigating the status of fat cell beta-adrenoceptors in various pathophysiological situations.

Adipose Tissue↗
PubMed1985

Direct assessment of beta-adrenergic receptors in intact rat adipocytes by binding of [3H]CGP 12177. Evidence for agonist high-affinity binding complex and for beta 1 and beta 2 receptor subtypes.

The characteristics of the binding of the hydrophilic beta-adrenergic antagonist [3H]CGP 12177 to intact rat adipocytes were studied at 37 degrees C and 6 degrees C. At both temperatures and at 90% saturation, the non-specific binding was less than 30% of the total binding. At 37 degrees C, specific [3H]CGP 12177 binding was rapid, reversible of high affinity (1.8 +/- 0.4 nM) and saturable. The number of specific binding sites per adipocyte increased with the fat cell size (about 35 000 and 115 000 sites per cell in adipocytes with diameters of 60 microns and 88 microns, respectively) but remained constant when expressed per unit fat cell surface area. Displacement of [3H]CGP 12177 bound to adipocytes by unselective and selective beta-antagonists was stereospecific, had the same characteristics as those found in adipocyte membranes and showed a heterogeneous specificity for beta 1 and beta 2 adrenergic subtypes. In contrast, beta agonist competition curves, which modeled to two affinity-states of binding, showed high-affinity-state Kd values for agonists 10-25-times higher than those found in membranes under the same experimental conditions. At 6 degrees C, although the number and affinity of the specific binding sites for [3H]CGP 12177 were the same as those found at 37 degrees C, the Kd value for (-)-isoproterenol binding to the high affinity state of these sites (3.0 +/- 0.5 nM) was 25-times lower than at 37 degrees C and similar to the value found in membrane preparations (1.5-4 nM). These results show that the [3H]CGP 12177 specific binding sites detected on intact adipocytes represent the physiological beta-adrenergic receptors. Moreover, this study extends to the adipocyte the validity of the model recently proposed for other cell lines, according to which in intact cells, but not in membranes, agonist-binding promotes a rapid and temperature-dependent conformational change of the beta-adrenergic receptors, leading to a progressive loss of capacity of agonists to form a high-affinity complex.

Adipose Tissue↗
PubMed1984

Stimulatory effects of adenosine, adenosine analogs and insulin on adipose tissue lipoprotein lipase activity and their prevention by phosphodiesterase inhibitors.

Adenosine and its 'Ri'- and 'P'-site analogs, N6-phenylisopropyladenosine and 2'-deoxyadenosine, stimulate, like insulin, lipoprotein lipase (LPL) activity in adipose tissue, an effect which is suppressed by cycloheximide. However, adenosine and its analogs do not potentiate the effects of submaximal insulin concentrations. As addition of cyclic AMP phosphodiesterase inhibitors abolishes the LPL stimulatory effects of insulin, adenosine and its analogs, this study suggests that these LPL effects are mediated through common mechanisms which are likely a decrease in cyclic AMP and an increase in LPL biosynthesis.

Adenosine↗
PubMed1984

Guanine nucleotides and adenosine "R(i)'-site analogues stimulate the membrane-bound low-K(m) cyclic AMP phosphodiesterase of rat adipocytes.

Concentrations of GTP or Gpp(NH)p up to 300 nM activated the membrane-bound low-K(m) cyclic AMP phosphodiesterase of rat adipocytes, while higher concentrations of these nucleotides reversed this activation. The adenosine analog N6-phenylisopropyladenosine (N6-PIA) elicited a dose-dependent stimulation of this enzyme (K(act) = 3 nM), an effect which did not require GTP and which was additive with the GTP-induced stimulation. Both the N6-PIA and GTP stimulations were rapid, reversible and resulted from an increase in V(max). In contrast, neither GTP, nor N6-PIA affected the soluble low-K(m) cyclic AMP phosphodiesterase.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1984

N6-phenylisopropyladenosine stimulates in normal and inhibits in adrenalectomized rats the low KM cyclic AMP phosphodiesterase in the brain.

In crude rat brain membranes, apparent adenylate cyclase activity tested in the absence of phosphodiesterase inhibitors was dose-dependently inhibited by the adenosine 'R-site' agonist N6-phenylisopropyladenosine (N6-PIA). In membranes from adrenalectomized rats, however, N6-PIA induced, under the same conditions, an activation. However, in the presence of the phosphodiesterase inhibitor Ro-20-1724, brain adenylate cyclase responsiveness to N6-PIA resulted in a dose-dependent inhibition in both sham-operated and adrenalectomized rats. Thus, the low KM cyclic AMP phosphodiesterase activity present in these brain membranes was investigated. Although this activity (tested in the presence of GTP) was unaltered by adrenalectomy, the dose-response curve of this enzyme to low concentrations of N6-PIA showed an activation in sham-operated and an inhibition in adrenalectomized rats, two effects which were suppressed by sodium (80 mM). These results showing that N6-PIA modulates both adenylate cyclase and cyclic AMP phosphodiesterase in the brain, provide an additional argument for a potential role of adenosine in the regulation of cyclic AMP metabolism in normal as well as in pathological brain.

3',5'-Cyclic-AMP Phosphodiesterases↗