Mineralocorticoid Receptor-Like Aldosterone-Binding Protein in Cell Culture*

Lan, Nancy C.; Matulich, Daniel T.; Morris, Julie; Baxter, John D.

doi:10.1210/endo-109-6-1963

Cited by 35 publications

(5 citation statements)

References 21 publications

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“…Prednisolone, like dexamethasone, can bind to MR in vitro, but the affinity to this receptor is much lower than to GR to which these steroids bind with very high affinity (<1 nM) (Lan et al 1981, De Kloet et al 1984. In contrast, corticosterone and cortisol bind with high affinity to MR (<1 nM) and with tenfold lower affinity to GR.…”

Section: Discussionmentioning

confidence: 99%

The role of the efflux transporter P-glycoprotein in brain penetration of prednisolone

Karssen¹,

Meijer²,

Sandt³

et al. 2002

Journal of Endocrinology

102

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In the present study, we have investigated the role of the multidrug resistance (mdr) P-glycoprotein (Pgp) at the blood-brain barrier in hampering the access of the synthetic glucocorticoid, prednisolone.In vivo, a tracer dose of [ 3 H]prednisolone poorly penetrated the brain of adrenalectomised wild-type mice, but the uptake was more than threefold enhanced in the absence of Pgp expression in mdr1a ( / ) mice. In vitro, in stably transfected LLC-PK1 monolayers the human MDR1 P-glycoprotein was able to transport prednisolone present at a micromolar concentration. A specific Pgp blocker, LY 335979, could block this polar transport of The ability of Pgp to export the synthetic glucocorticoid, prednisolone, suggests that uptake of prednisolone in the human brain is impaired, leading to a discrepancy between central and peripheral actions. Furthermore, the ensuing imbalance in activation of the two types of brain corticosteroid receptors may have consequences for cognitive performance and mood.

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Section: Discussionmentioning

confidence: 99%

The role of the efflux transporter P-glycoprotein in brain penetration of prednisolone

Karssen¹,

Meijer²,

Sandt³

et al. 2002

Journal of Endocrinology

102

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“…In confirma tion of reports on the kidney [16], the nervous system [2, 3. 40], and other tissue sources [20,22,23], high affinity (Kd < 1 n M ) as well as low affinity (Kd 30-195 nM ) binding sites were detected in the SC by saturation analysis. The nature of these binding sites was investigated employing antagon ists of the glucocorticoid and the mineralocorticoid recep tors [3, 7, 8, 22, 28, 30, 34.…”

Section: Discussionmentioning

confidence: 99%

Evidence of High Affinity, Stereoselective Binding Sites for [<sup>3</sup>H]-Aldosterone in the Spinal Cord

Ortí¹,

Magariños²,

Nicola³

1986

Neuroendocrinology

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Cytosol from the spinal cord (SC) of adrenalectomized rats was incubated with a range of [³H]-aldosterone (ALDO) concentrations and the results analyzed according to Scatchard. High affinity (Kd < 1 nM) as well as low affinity (Kd 30–195 nM) sites were measured; the low affinity site was abolished by co-incubation with the pure antiglucocorticoid RU 28362. [³H]-ALDO in concentrations shown to bind to the high affinity site only, was completely displaced by the spirolactone, RU 26752, but not by RU 28362; however, the latter compound competed for 40% of the sites when incubated with a higher (10 nM) concentration of [³H]-ALDO, binding approximately one-half to each receptor type. The high affinity site was distributed uniformly in four sections of the SC, with significantly lower levels in the region corresponding to the filum terminale and horse tail and slightly higher in the cervical and lumbar enlargements. The high affinity site acquired increased affinity for DNA-cellulose after heat-induced transformation, with reduced capacity to bind to DEAE-cellulose. These results suggest that the SC contains, in addition to glucocorticoid receptors, binding molecules of high affinity and stereoselectivity for mineralocorticoids, and that, under appropriate conditions, present increased affinity for DNA acceptor sites.

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“…A few studies have directly compared cortisol, prednisolone, and dexamethasone using the same experimental assays. In studies examining rat MR, prednisolone and cortisol have similar affinities for this receptor (C 50 =20 nM for prednisolone and 16 nM for cortisol) (Lan et al 1981) and similar abilities to inhibit sodium excretion in adrenalectomized rats, an index of MR activity (Liddle 1958), while dexamethasone has a 3.5-fold lower affinity (C 50 =57 nM) for the MR (Lan et al 1981) and shows no activity in the sodium excretion assay (Slater et al 1959).…”

Section: Introductionmentioning

confidence: 99%

Different responses to dexamethasone and prednisolone in the same depressed patients

et al. 2006

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Mineralocorticoid Receptor-Like Aldosterone-Binding Protein in Cell Culture*

Cited by 35 publications

References 21 publications

The role of the efflux transporter P-glycoprotein in brain penetration of prednisolone

The role of the efflux transporter P-glycoprotein in brain penetration of prednisolone

Evidence of High Affinity, Stereoselective Binding Sites for [<sup>3</sup>H]-Aldosterone in the Spinal Cord

Different responses to dexamethasone and prednisolone in the same depressed patients

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