Glucocorticoid antagonists

Agarwal, M.K.; Hainque, Bernard; Moustaïd, N.; Lazer, G.

doi:10.1016/0014-5793(87)80667-1

Cited by 36 publications

(8 citation statements)

References 69 publications

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“…Both Dex and RU38486 bind to the membrane‐bound glucocorticoid receptor (Chen et al ., 1993; Quelle et al ., 1988) but the binding‐affinity of RU38486 is greater than that of Dex (Chen et al ., 1993). RU38486 also has a high affinity for the cytosolic glucocorticoid receptor and is a reliable competitive antagonist of this receptor (Agarwal et al ., 1987). This compound has no agonist activity at either receptor.…”

Section: Methodsmentioning

confidence: 99%

Dexamethasone attenuates the depressor response induced by neuropeptide Y microinjected into the nucleus tractus solitarius in rats

Ouyang

Shao

2000

British J Pharmacology

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1 An investigation was made of the eect of dexamethasone (Dex) injection into the nucleus tractus solitarius (NTS) on the cardiovascular response to neuropeptide Y in rats. 2 Dex (39 pmol) injected into the NTS inhibited the hypotension and bradycardia caused by NPY (5 pmol) with a short latency (10 min) and a long duration of action (up to 4 h). 3 The rapid inhibition by Dex (39 pmol) of the cardiovascular response to NPY was not blocked by pretreatment with the glucocorticoid receptor blocker, RU38486 (47 or 117 pmol respectively), but was reversed by bicuculline (30 pmol). 4 Microiontophoresis of NPY (0.01 mM, pH 6.5) into the NTS increased the spontaneous ®ring of the majority (68.4%) of barore¯ex-excited cells, but decreased the ®ring of most (73.7%) barore¯ex-inhibited cells. In contrast, Dex (0.02 M, pH 6.5) decreased the spontaneous ®ring of the majority of barore¯ex-excited cells (42.1% of normal response) and decreased the inhibition of barore¯ex-inhibited cells (47.5% of normal response). The responses of the majority of baroreceptive cells to NPY were blocked by iontophoretic administration of Dex. 5 Dex (200 mM) increased the delayed recti®er outward K+ current by 31.4+1.1% (n=5), whereas NPY alone, at a concentration of 1.5 mM, inhibited the current by 28.6+0.8% (n=5). In the presence of Dex (200 mM), addition of NPY (1.5 mM) had no eect on the current. 6 In conclusion, NTS-administered-Dex attenuated the cardiovascular response to NPY injected into the same area via a rapid membrane eect, which was mediated by an action on GABA A receptors and on the delayed recti®er outward K + channel.

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Section: Methodsmentioning

confidence: 99%

Dexamethasone attenuates the depressor response induced by neuropeptide Y microinjected into the nucleus tractus solitarius in rats

Ouyang

Shao

2000

British J Pharmacology

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“…However, the regulatory mechanisms of fatty acid biosynthesis are still poorly understoocL We have demonstrated that the regulatory action of gluc~ corticoid hormones on the fatty acid desaturase activities depends on a protein factor whose biosynthesis is brought about by hormonal induction (1,3). Although ll<leoxycorticosterone (DOC) does not have an 11-/Y-hydroxy group, which is thought to be essential for glucocorticoid activity (6), we have previously demonstrated that in HTC cells this hormone can induce a soluble regulatory factor that stimu-lares A9 desaturase activity (7). Two species of adrenoco~ tical hormone receptors have been definecE i) Those receptom associated with mineralocorticoid function which have a high affinity for aldosterone (ALDO) and a lower affinity for corticosterone (8); and ii) those receptors associated with glucocorticoid function which have a high affinity for cot ~ ticosterone and a lower affinity for aldosterone (9,10).…”

Section: Lipids 27 599-604 (1992)mentioning

confidence: 99%

Glucocorticoid and mineralocorticoid hormones depress liver Δ5 desaturase activity through different mechanisms

Alaniz

Marra

1992

Lipids

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The effects of 11-deoxycorticosterone and aldosterone on liver delta 5 desaturase activity were examined. Both steroid hormones significantly depressed the conversion of [1-14C] eicosatrienoic acid to arachidonic acid. However, the mechanism of action of each of these hormones was different. The effect of 11-deoxycorticosterone was mediated by a soluble protein present in the liver cytosolic fraction. The biological activity of this protein, having a molecular weight lower than 25 kDa, was impaired by trypsin digestion. To determine whether the inhibitory protein was induced through glucocorticoid or mineralocorticoid receptor occupancy, cultured Morris minimal deviation hepatoma cells were pre-treated with the antiglucocorticoid cortexolone or the mineralocorticoid receptor antagonist spironolactone. The results obtained demonstrated that only glucocorticoid receptor structures were involved in the induction of this regulatory protein. The inhibitory response evoked by aldosterone was mediated by a different mechanism. In the case of aldosterone, the inhibitory action affected the microsomal membranes and was not mediated by a soluble protein messenger.

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“…RU 38486 has a high affinity to glucocorticoid's cytosolic receptor but has no agonist effect, so it is a competitive antago nist of glucocorticoid receptor [ 1 ]. RU 38486 alone exerted no influences on either membrane potential or input resistance of the cell.…”

Section: Intracellular Microelectrode Study On Isolated Coeliac Ganglmentioning

confidence: 99%

An Electrophysiological Study on the Membrane Receptor-Mediated Action of Glucocorticoids in Mammalian Neurons

et al. 1991

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The action of glucocorticoids (GC) on neuronal cell membrane was studied in isolated and superfused guinea pig coeliac ganglia by the intracellular recording technique. Cortisol succinate (F) hyperpolarized the membrane potential of 47 of 179 cells and changed the cell’s input resistance with a latency of less than 2 min in vitro. The effect persisted under low Ca²⁺/high Mg²⁺ superfusing condition and could be blocked by RU 38486, a competitive antagonist of GC cytosolic receptor. Cortisol-21-bovine albumin conjugant exhibited the same effect. Corticosterone (B) elicited hyperpolarization in another 15 of 83 cells, but dexamethasone (Dex) did not. Dex, however, depolarized 2 of 18 cells. Aldosterone, cholesterol and vehicle (ethyl alcohol) caused no detectable change in membrane potential. In vivo studies by iontophoretic application of steroids to hypothalamic paraventricular (PVN) neurons showed that F inhibited the unit discharges in 68 of 97 PVN neurons, and the effect could be antagonized by RU 38486. Dex excited 30 of 100 neurons. Estradiol (E) also inhibited the discharges, but this inhibition was not antagonized by RU 38486. The effect of GC on PVN neurons was also examined in hypothalamic slices including the paraventricular nucleus. B inhibited 28 of 104 units and excited 7 of 104 cells, and both effects could be antagonized by RU 38486. The threshold of inhibitory response was about 10^–7M, which is close to the physiological level of the hormone in plasma. The results suggest that GC can act non-genomically and specifically through its membrane receptor on the neuronal surface, and that there might be a chemical similarity between the membrane receptor and the traditional cytosolic GC receptor. It is also suggested that the modulatory action of GV might have some important physiological significance.

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Glucocorticoid antagonists

Cited by 36 publications

References 69 publications

Dexamethasone attenuates the depressor response induced by neuropeptide Y microinjected into the nucleus tractus solitarius in rats

Dexamethasone attenuates the depressor response induced by neuropeptide Y microinjected into the nucleus tractus solitarius in rats

Glucocorticoid and mineralocorticoid hormones depress liver Δ5 desaturase activity through different mechanisms

An Electrophysiological Study on the Membrane Receptor-Mediated Action of Glucocorticoids in Mammalian Neurons

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