Non-genomic effects of steroids Interactions of steroid molecules with membrane structures and functions

Duval, Dominique; Durant, Sylvie; Homo‐Delarche, Françoise

doi:10.1016/0304-4157(83)90008-4

Cited by 252 publications

(80 citation statements)

References 278 publications

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“…The proposed mechanisms of inhaled glucocorticosteroids include upregulation of selective b-adrenergic receptors, vasoconstriction of the mucosa and decreased wall oedema within the airway [27]. However, the rapid onset of the clinical response in some of these clinical studies [7,9] would indicate that some beneficial effects of glucocorticosteroids may occur very rapidly, while other effects may occur very slowly, requiring a minimum of 6-12 h after medication [28].…”

Section: Discussionmentioning

confidence: 99%

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Fluticasone propionate attenuates platelet-activating factor-induced gas exchange defects in mild asthma

Acuña¹,

Gabrijelcic²,

Uribe

et al. 2002

Eur Respir J

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Inhaled glucocorticosteroids may reduce airway mucosal oedema in acute asthma. Inhaled platelet-activating factor (PAF) provokes pulmonary gas exchange disturbances, similar to those shown in severe asthma, which may be due to increased airway plasma leakage.This randomized, double-blind, placebo-controlled, crossover study investigated the effects of high doses of inhaled fluticasone propionate (FP) in 12 patients with mild asthma before and after PAF inhalation. Patients were studied before and 12 h after inhaling FP (6 mg) or placebo (P), and then at 5, 15 and 45 min after PAF challenge.Compared with vehicle, FP inhaled before PAF improved forced expiratory volume in one second and respiratory system resistance (Rrs), increased peripheral blood neutrophils and reduced eosinophil counts. After PAF, FP enhanced transient neutropenia at 5 min and facilitated the recovery of oxygen tension in arterial blood (FP: 93¡4 mmHg; P: 83¡4 mmHg) at 45 min, without influencing the increases in Rrs.In conclusion, the improvement of platelet-activated factor-induced oxygen tension in arterial blood disturbances after fluticasone proprionate suggests that inhaled glucocorticosteroids may possess vasoconstrictor properties in the pulmonary circulation.

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Section: Discussionmentioning

confidence: 99%

“…It has been postulated that this vascular response may reflect a nongenomic mode of action [9,27] related to stimulation of noradrenergic neurotransmission. However, glucocorticosteroids do not exhibit direct noradrenergic properties.…”

Section: Discussionmentioning

confidence: 99%

Fluticasone propionate attenuates platelet-activating factor-induced gas exchange defects in mild asthma

Acuña¹,

Gabrijelcic²,

Uribe

et al. 2002

Eur Respir J

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“…Early investigations dating back to the 1940s showed that certain effects occur within only a few minutes, a time frame that would seem to preclude genomic-mediated responses (Duval et al 1983). We have proposed for the first time that the member-receptor mediated rapid effects of GCs exist on mammalian neurons (Chen et al 1987).…”

Section: Introductionmentioning

confidence: 99%

Rapid nongenomic effects of glucocorticoids on allergic asthma reaction in the guinea pig

Zhou¹,

Kang²,

Xie³

et al. 2003

Journal of Endocrinology

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Glucocorticoids (GCs) are routinely believed to work solely through genomic mechanisms. Recent evidence indicates that GCs can act at the membrane to exert rapid nongenomic effects on various tissues and cells. To ascertain whether nongenomic effects of GCs exist on the allergic asthma reaction, Hartley guinea pigs were sensitized with ovalbumin and challenged with the same antigen given by aerosol. Some animals received inhaled budesonide (3 mg/ml suspended in Hydroxypropyl methylcellulose vehicle) for 5 minutes before ovalbumin challenge; Other animals received saline or blank vehicle as control. We measured the changes of lung resistance and dynamic lung compliance, the pulmonary function used to evaluate allergic asthma severity. Inhaled budesonide inhibited allergic reaction within 10 minutes, which would preclude genomic-mediated responses that normally takes several hours to occur. This study infers for the first time that rapid nongenomic effect of GCs exists on allergic asthma reaction, and provides a new way to investigate nongenomic mechanism of GCs. Further study would raise the possibility of new therapeutic strategies for allergic disease including asthma.

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“…These signals could mean that there are distinct nongenomic pathways for the action of these two steroids in skeletal muscle cells. steroid hormones; inositol 1,4,5-trisphosphate; calcium waves; nongenomic pathway STEROID HORMONES ARE CAPABLE of producing rapid (within 2 min) effects in several cell types (12,22,36). These rapid responses are not compatible with the classical mechanism of action proposed for these hormones, which involves binding to intracellular receptors, transcriptional processes, and protein synthesis (1, 20).…”

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confidence: 99%

Aldosterone- and testosterone-mediated intracellular calcium response in skeletal muscle cell cultures

Estrada

Liberona

Miranda

et al. 2000

American Journal of Physiology-Endocrinology and Metabolism

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] i was monitored in Fluo 3-acetoxymethyl esterloaded myotubes by either confocal microscopy or fluorescence microscopy, with the use of out-of-focus fluorescence elimination. The mass of IP 3 was determined by radioreceptor displacement assay. [Ca 2ϩ ] i changes after either aldosterone (10-100 nM) or testosterone (50-100 nM) were observed; a relatively fast (Ͻ2 min) calcium transient, frequently accompanied by oscillations, was evident with both hormones. A slow rise in [Ca 2ϩ ] i that reached its maximum after a 30-min exposure to aldosterone was also observed. Calcium responses seem to be fairly specific for aldosterone and testosterone, because several other steroid hormones do not induce detectable changes in fluorescence, even at 100-fold higher concentrations. The mass of IP 3 increased transiently to reach two-to threefold the basal level 45 s after addition of either aldosterone or testosterone, and the IP 3 transient was more rapid than the fast calcium signal. Spironolactone, an inhibitor of the intracellular aldosterone receptor, or cyproterone acetate, an inhibitor of the testosterone receptor, had no effect on the fast [Ca 2ϩ ] i signal or in the increase in IP 3 mass. These signals could mean that there are distinct nongenomic pathways for the action of these two steroids in skeletal muscle cells. steroid hormones; inositol 1,4,5-trisphosphate; calcium waves; nongenomic pathway STEROID HORMONES ARE CAPABLE of producing rapid (within 2 min) effects in several cell types (12,22,36). These rapid responses are not compatible with the classical mechanism of action proposed for these hormones, which involves binding to intracellular receptors, transcriptional processes, and protein synthesis (1, 20). Thus, for rapid steroid effects, the existence of membrane receptors for steroids has been proposed (2, 37). In skeletal muscle, steroid hormones have long been known to modulate gene expression, and hormones like testosterone have been related to both muscle hypertrophy (4, 25) and upregulation of a number of proteins (31). In particular, glucocorticoids and mineralocorticoids have been related to up-and downregulation, respectively, of sodium pumps in skeletal muscle (10), implying the presence of steroid hormone receptors in muscle cells. Because all these effects have been the result of chronic (hours to days) treatments, it would be interesting to know whether exposure to these hormones is also accompanied by fast nongenomic events.The signal transduction mechanism for the rapid action of steroids in some cellular models could be regulated by second messengers such as intracellular calcium ([Ca 2ϩ

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Non-genomic effects of steroids Interactions of steroid molecules with membrane structures and functions

Cited by 252 publications

References 278 publications

Fluticasone propionate attenuates platelet-activating factor-induced gas exchange defects in mild asthma

Fluticasone propionate attenuates platelet-activating factor-induced gas exchange defects in mild asthma

Rapid nongenomic effects of glucocorticoids on allergic asthma reaction in the guinea pig

Aldosterone- and testosterone-mediated intracellular calcium response in skeletal muscle cell cultures

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