Correlation between pregnanesteroid conformation, receptor affinity, and anti-natriuretic effect

The aim of this study was to correlate mineralocorticoid action and steroid structure. Inasmuch as Na+ retention follows a parabolic dose-response curve for most pregnanesteroids, the second-order coefficient of the function was used as a representative factor for this bipartite biological effect. T...

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Autor principal: Piwien-Pilipuk, G.
Otros Autores: Kanelakis, K.C, Galigniana, M.D
Formato: Capítulo de libro
Lenguaje:Inglés
Publicado: 2002
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Acceso en línea:Registro en Scopus
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024 7 |2 scopus  |a 2-s2.0-0037111505 
024 7 |2 cas  |a Pregnanes; Receptors, Mineralocorticoid 
040 |a Scopus  |b spa  |c AR-BaUEN  |d AR-BaUEN 
030 |a EJPHA 
100 1 |a Piwien-Pilipuk, G. 
245 1 0 |a Correlation between pregnanesteroid conformation, receptor affinity, and anti-natriuretic effect 
260 |c 2002 
270 1 0 |m Galigniana, M.D.; 1301 Med. Sci. Research Building III, Department of Pharmacology, Univ. of Michigan Medical School, Ann Arbor, MI 48109-0632, United States; email: mgali@umich.edu 
506 |2 openaire  |e Política editorial 
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504 |a Burton, G., Galigniana, M.D., DeLavallaz, S., Brachet-Cota, A.L., Sproviero, E.M., Ghini, A.A., Lantos, C.P., Sodium-retaining activity of some natural and synthetic 21-deoxysteroids (1995) Mol. Pharmacol., 47, pp. 535-543 
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504 |a Dluhy, R.G., Glucocorticoid-remediable aldosteronism (2001) Endocrinologist, 11, pp. 263-268 
504 |a Fagart, J., Wurtz, J.M., Souque, A., Hellal-Levy, C., Moras, D., Rafestin-Oblin, M.E., Antagonism in the human mineralocorticoid receptor (1998) EMBO J., 17, pp. 3317-3325 
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504 |a Funder, J.W., Aldosterone and mineralocorticoid receptors: Orphan questions (2000) Kidney Int., 57, pp. 1358-1363 
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504 |a Galigniana, M.D., Native rat kidney mineralocorticoid receptor is a phosphoprotein whose transformation to a DNA-binding form is induced by phosphatases (1998) Biochem. J., 333, pp. 555-563 
504 |a Galigniana, M.D., Functional regulation of corticosteroid receptors by phosphorylation and redox potential (2000) Curr. Top. Steroid Res., 3, pp. 1-22 
504 |a Galigniana, M.D., Piwien-Pilipuk, G., Comparative inhibition by hard and soft metal ions on steroid-binding capacity of renal mineralocorticoid receptor cross-linked to the 90-kDa heat-shock protein heterocomplex (1999) Biochem. J., 341, pp. 585-592 
504 |a Galigniana, M.D., Vicent, G.P., Lantos, C.P., Burton, G., Ligand properties of 11,19-oxidoprogesterone: A preliminary report (1993) An. Asoc. Quím. Argent., 81, pp. 333-340 
504 |a Galigniana, M.D., Vicent, G.P., Burton, G., Lantos, C.P., Features of the shuttle pair 11β-hydroxyprogesterone/11-ketoprogesterone (1997) Steroids, 62, pp. 358-364 
504 |a Galigniana, M.D., Vicent, G.P., Piwien-Pilipuk, G., Burton, G., Lantos, C.P., Mechanism of action of the potent sodium-retaining steroid 11,19-oxidoprogesterone (2000) Mol. Pharmacol., 58, pp. 58-70 
504 |a Grassy, G., Fagart, J., Calas, B., Adenot, M., Rafestin-Oblin, M.E., Auzou, G., Structure-activity relationships of steroids with mineralocorticoid activity (1997) Eur. J. Med. Chem., 32, pp. 869-879 
504 |a Koshida, H., Miyamori, I., Soma, R., Matsubara, T., Ikeda, M., Takeda, R., Nakamura, S., Tsuda, Y., Mineralocorticoid and renal receptor binding activity of 21-deoxyaldosterone (1990) Endocrinology, 126, pp. 1410-1415 
504 |a Lantos, C.P., Burton, G., Roldán, A., Damasco, M.C., Aragonés, A., Structure-activity relationship in certain glucocorticoids and mineralocorticoids (1981) Physiopathology of Endocrine Diseases and Mechanisms of Hormone Action, pp. 477-494. , R.J. Soto, A. de Nicola, & J. Blaquier. New York: Alan R. Liss 
504 |a Lombès, M., Kenouch, S., Souque, A., Farman, N., Rafestin-Oblin, M.E., The mineralocorticoid receptor discriminates aldosterone from glucocorticoids independently of the 11β-hydroxysteroid dehydrogenase (1994) Endocrinology, 135, pp. 834-840 
504 |a Piwien-Pilipuk, G., Galigniana, M.D., Tautomycin inhibits phosphatase-dependent transformation of the rat kidney mineralocorticoid receptor (1998) Mol. Cell. Endocrinol., 144, pp. 119-130 
504 |a Piwien-Pilipuk, G., Kanelakis, K.C., Ghini, A.A., Lantos, C.P., Litwack, G., Burton, G., Galigniana, M.D., Modification of an essential amino group in the mineralocorticoid receptor evidences a differential conformational change of the receptor protein upon binding of antagonists, natural agonists and the synthetic agonist 11,19-oxidoprogesterone (2001) Biochim. Biophys. Acta, 1589, pp. 31-48 
504 |a Robertson, N.M., Schulman, G., Karnik, S., Alnemri, E., Litwack, G., Demonstration of nuclear translocation of the mineralocorticoid receptor (MR) using anti-MR antibody and confocal scanning microscopy (1993) Mol. Endocrinol., 7, pp. 1226-1239 
504 |a Sheppard, K.E., Funder, J.W., Type I receptors in parotid, colon and pituitary are aldosterone-selective in vivo (1987) Am. J. Physiol., 253, pp. E467-E471 
504 |a Souque, A., Fagart, J., Coutte, B., Davioud, E., Marquet, A., Rafestin-Oblin, M.E., The mineralocorticoid activity of progesterone derivatives depends on the nature of the C18 substituent (1995) Endocrinology, 136, pp. 5651-5658 
504 |a Struhl, K., Histone acetylation and transcriptional regulatory mechanisms (1998) Genes Dev., 12, pp. 599-606 
504 |a Teutsch, G., Nique, F., Lemoine, G., Bouchoux, F., Cérède, E., Gofflo, D., Philibert, D., General structure-activity correlations of antihormones (1995) Ann. N.Y. Acad. Sci., 761, pp. 5-28 
504 |a Veleiro, A.S., Nevado, M.V., Monteserín, M.C., Burton, G., Syntheses of 21-hydroxy-11,19-oxidopregn-4-ene-3,20-dione and 21-hydroxy-6,19-oxidopregn-4-ene-3,20-dione (1995) Steroids, 60, pp. 358-364 
504 |a Young, D.B., Quantitative analysis of aldosterone's role in potassium regulation (1988) Am. J. Physiol., 255, pp. F811-F822 
520 3 |a The aim of this study was to correlate mineralocorticoid action and steroid structure. Inasmuch as Na+ retention follows a parabolic dose-response curve for most pregnanesteroids, the second-order coefficient of the function was used as a representative factor for this bipartite biological effect. The C3=O/D angle of the ligands was correlated with both Na+-retaining activity and binding affinity for the mineralocorticoid receptor. Because some steroids exhibit identical functional groups and different conformational structure, we also postulate that the flat conformation of a pregnanesteroid determines its Na+-retaining capacity in vivo. No correlations were found in vitro, which demonstrates the multifactorial nature of the second-order coefficient determined in vivo under more complex and interactive conditions that include various pre-receptor variables. These findings may allow the estimation of the putative biological activity of a given steroid simply by knowing its conformational structure, which may be important for designing compounds in a pharmaceutical setting. © 2002 Elsevier Science B.V. All rights reserved.  |l eng 
593 |a Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, 1428, Buenos Aires, Argentina 
593 |a Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI 48109, United States 
593 |a 1301 Medical Science Research Building III, Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI 48109-0632, United States 
690 1 0 |a ALDOSTERONE 
690 1 0 |a MINERALOCORTICOID RECEPTOR 
690 1 0 |a NATRIURESIS 
690 1 0 |a STEROID CONFORMATION 
690 1 0 |a 11BETA,17BETA DIHYDROXY 6 METHYL 17ALPHA (1 PROPYNYL)ANDROSTA 1,4,6 TRIEN 3 ONE 
690 1 0 |a FUNCTIONAL GROUP 
690 1 0 |a LIGAND 
690 1 0 |a MINERALOCORTICOID RECEPTOR 
690 1 0 |a PREGNANE DERIVATIVE 
690 1 0 |a PREGNANESTEROID 
690 1 0 |a SODIUM ION 
690 1 0 |a STEROID 
690 1 0 |a UNCLASSIFIED DRUG 
690 1 0 |a MINERALOCORTICOID RECEPTOR 
690 1 0 |a PREGNANE DERIVATIVE 
690 1 0 |a ANIMAL CELL 
690 1 0 |a ANIMAL EXPERIMENT 
690 1 0 |a ANTIDIURESIS 
690 1 0 |a ARTICLE 
690 1 0 |a BINDING AFFINITY 
690 1 0 |a CONCENTRATION RESPONSE 
690 1 0 |a CONTROLLED STUDY 
690 1 0 |a CORRELATION ANALYSIS 
690 1 0 |a DRUG CONFORMATION 
690 1 0 |a DRUG MECHANISM 
690 1 0 |a DRUG RECEPTOR BINDING 
690 1 0 |a DRUG STRUCTURE 
690 1 0 |a IN VITRO STUDY 
690 1 0 |a IN VIVO STUDY 
690 1 0 |a MALE 
690 1 0 |a NONHUMAN 
690 1 0 |a PRIORITY JOURNAL 
690 1 0 |a SODIUM RETENTION 
690 1 0 |a ANIMAL 
690 1 0 |a CELL STRAIN COS1 
690 1 0 |a CERCOPITHECUS 
690 1 0 |a CHEMISTRY 
690 1 0 |a DOSE RESPONSE 
690 1 0 |a DRUG EFFECT 
690 1 0 |a HUMAN 
690 1 0 |a METABOLISM 
690 1 0 |a NATRIURESIS 
690 1 0 |a PHYSIOLOGY 
690 1 0 |a PROTEIN BINDING 
690 1 0 |a RAT 
690 1 0 |a SPRAGUE DAWLEY RAT 
690 1 0 |a STRUCTURE ACTIVITY RELATION 
690 1 0 |a ANIMALS 
690 1 0 |a CERCOPITHECUS AETHIOPS 
690 1 0 |a COS CELLS 
690 1 0 |a DOSE-RESPONSE RELATIONSHIP, DRUG 
690 1 0 |a HUMANS 
690 1 0 |a MALE 
690 1 0 |a NATRIURESIS 
690 1 0 |a PREGNANES 
690 1 0 |a PROTEIN BINDING 
690 1 0 |a RATS 
690 1 0 |a RATS, SPRAGUE-DAWLEY 
690 1 0 |a RECEPTORS, MINERALOCORTICOID 
690 1 0 |a STRUCTURE-ACTIVITY RELATIONSHIP 
653 0 0 |a ru 28362, Roussel Uclaf, France 
700 1 |a Kanelakis, K.C. 
700 1 |a Galigniana, M.D. 
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