Mineralocorticoid receptor gene expression in the gastrointestinal tract: Distribution and ontogeny

Fuller, Peter J.; Verity, Karen

doi:10.1016/0022-4731(90)90215-e

Cited by 47 publications

(15 citation statements)

References 26 publications

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“…Similar doses of GC and MC were used, yet the specificity was preserved. The finding that, in tissue with low MC receptors (kidney) (41) or aldosteroneindependent tissue (stomach) (42), the Na,K-ATPase mRNA increased rapidly after GC in a similar manner seems to indicate that the GC receptor and not the MC receptor mediates the response. However, the observation that, in a tissue such as the brain where both Na,K-ATPase and GC receptors are abundant and ubiquitous (43, 44), GC did not stimulate an increase in Na,K-ATPase mRNA seems to indicate that other factors are necessary in addition to the GC receptor.…”

Section: Control Betamethasonementioning

confidence: 98%

“…The activity of colon Na,K-ATPase is low in infancy, and both aldosterone and GC have been shown to stimulate maturation of the enzyme activity (4,19). The rat distal colon contains abundant MC and GC receptors which are expressed in epithelial surface and crypt cells (20,21). Thus, the colon is an excellent model in which to study the specific rolc of GC and MC in the maturation of epithelial ion transporters.…”

mentioning

confidence: 99%

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Differential Effects of Glucocorticoids and Mineralocorticoids on the mRNA Expression of Colon Ion Transporters in Infant Rats

1995

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Several epithelial ion transporters are developmentally regulated in the preweaning period, at the time when the circulating levels of glucocorticoid and mineralocorticoid hormones increase. The specific role of glucocorticoids and mineralocorticoids in thc maturation of epithelial ion transport is still disputed. In this study, we investigated the effect of corticosteroids on the mRNA expression of ion transporters in the infant rat colon, a glucocorticoid-and mineralocorticoid-sensitive organ. The expression of the Na,K-ATPase, the H,K-ATPase and the amiloride-sensitive Na+ channel mRNA was investigated in control rats from fctal to adult life. We found that the mRNA of the three transporters is temporarily up-regulated in the preweaning period. Rats were then injected with a single dose of betamethasone or aldosterone at 10 d of age. The main effect was the glucocor-

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Section: Control Betamethasonementioning

confidence: 98%

mentioning

confidence: 99%

Differential Effects of Glucocorticoids and Mineralocorticoids on the mRNA Expression of Colon Ion Transporters in Infant Rats

1995

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“…Similarly, the MR is expressed extensively in the central nervous system (CNS), and indeed, the hippocampus arguably has the highest abundance of MR of any tissue in the body with the possible exception of the distal colon (Fuller & Verity 1990). The function of the MR in the CNS has been the subject of extensive investigation (for a review, see Joëls et al (2007)); it appears to have fundamental roles in diverse behavioural responses including memory and affect.…”

Section: Non-epithelial Tissuesmentioning

confidence: 99%

Mechanisms of ligand specificity of the mineralocorticoid receptor

Fuller¹,

Yao²,

Yang³

et al. 2011

Journal of Endocrinology

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The mineralocorticoid receptor (MR) differs from the other steroid receptors in that it responds to two physiological ligands, aldosterone and cortisol. In epithelial tissues, aldosterone selectivity is determined by the activity of 11b-hydroxysteroid dehydrogenase type 2, while in other tissues, including the heart and regions of the central nervous system, cortisol is the primary ligand for the MR where it may act as an antagonist. Clinical trials have demonstrated the potential of MR antagonists in the treatment of cardiovascular disease, though their use has been limited by concurrent hyperkalaemia. In order to better target the MR, an understanding of the structural determinants of tissue-and ligand-specific MR activation is needed. Interactions of the MR have been identified, which exhibit ligand discrimination and/or specificity. These interactions include those of the ligand-binding domain with ligand, with the N-terminal domain and with putative co-regulatory molecules. Agonist and antagonist binding have been characterised using chimeras between the human MR and the glucocorticoid receptor or the zebra fish MR together with molecular modelling. The interaction between the N-terminus and the C-terminus is aldosterone dependent but is unexpectedly antagonised by cortisol and deoxycorticosterone in the human MR. Nuclear receptormediated transactivation is critically dependent on, and modulated by, co-regulatory molecules. Proteins that interact with the MR in the presence of either aldosterone or cortisol, but not both, have been identified. The successful identification of ligand-specific interactions of the MR may provide the basis for the development of novel MR ligands with tissue specificity.

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“…The mammalian colon is a major target for aldosterone, and the level of mineralocorticoid receptor gene expression is higher in the distal colon than in any other target tissue including the kidney [62,63]. In the distal colon, aldosterone causes a switch from electroneutral NaCl absorption to stimulated electrogenic Na + absorption by inducing expression of apical ENaC and basolateral Na + , K + -ATPase [64,65].…”

Section: Colonmentioning

confidence: 99%