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Abstract:

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.

Registro:

Documento: Artículo
Título:Correlation between pregnanesteroid conformation, receptor affinity, and anti-natriuretic effect
Autor:Piwien-Pilipuk, G.; Kanelakis, K.C.; Galigniana, M.D.
Filiación:Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, 1428, Buenos Aires, Argentina
Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI 48109, United States
1301 Medical Science Research Building III, Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI 48109-0632, United States
Palabras clave:Aldosterone; Mineralocorticoid receptor; Natriuresis; Steroid conformation; 11beta,17beta dihydroxy 6 methyl 17alpha (1 propynyl)androsta 1,4,6 trien 3 one; functional group; ligand; mineralocorticoid receptor; pregnane derivative; pregnanesteroid; sodium ion; steroid; unclassified drug; mineralocorticoid receptor; pregnane derivative; animal cell; animal experiment; antidiuresis; article; binding affinity; concentration response; controlled study; correlation analysis; drug conformation; drug mechanism; drug receptor binding; drug structure; in vitro study; in vivo study; male; nonhuman; priority journal; sodium retention; animal; cell strain COS1; Cercopithecus; chemistry; dose response; drug effect; human; metabolism; natriuresis; physiology; protein binding; rat; Sprague Dawley rat; structure activity relation; Animals; Cercopithecus aethiops; COS Cells; Dose-Response Relationship, Drug; Humans; Male; Natriuresis; Pregnanes; Protein Binding; Rats; Rats, Sprague-Dawley; Receptors, Mineralocorticoid; Structure-Activity Relationship
Año:2002
Volumen:454
Número:2-3
Página de inicio:131
Página de fin:143
DOI: http://dx.doi.org/10.1016/S0014-2999(02)02492-5
Título revista:European Journal of Pharmacology
Título revista abreviado:Eur. J. Pharmacol.
ISSN:00142999
CODEN:EJPHA
CAS:Pregnanes; Receptors, Mineralocorticoid
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00142999_v454_n2-3_p131_PiwienPilipuk

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Citas:

---------- APA ----------
Piwien-Pilipuk, G., Kanelakis, K.C. & Galigniana, M.D. (2002) . Correlation between pregnanesteroid conformation, receptor affinity, and anti-natriuretic effect. European Journal of Pharmacology, 454(2-3), 131-143.
http://dx.doi.org/10.1016/S0014-2999(02)02492-5
---------- CHICAGO ----------
Piwien-Pilipuk, G., Kanelakis, K.C., Galigniana, M.D. "Correlation between pregnanesteroid conformation, receptor affinity, and anti-natriuretic effect" . European Journal of Pharmacology 454, no. 2-3 (2002) : 131-143.
http://dx.doi.org/10.1016/S0014-2999(02)02492-5
---------- MLA ----------
Piwien-Pilipuk, G., Kanelakis, K.C., Galigniana, M.D. "Correlation between pregnanesteroid conformation, receptor affinity, and anti-natriuretic effect" . European Journal of Pharmacology, vol. 454, no. 2-3, 2002, pp. 131-143.
http://dx.doi.org/10.1016/S0014-2999(02)02492-5
---------- VANCOUVER ----------
Piwien-Pilipuk, G., Kanelakis, K.C., Galigniana, M.D. Correlation between pregnanesteroid conformation, receptor affinity, and anti-natriuretic effect. Eur. J. Pharmacol. 2002;454(2-3):131-143.
http://dx.doi.org/10.1016/S0014-2999(02)02492-5