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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todo:paper_00142999_v454_n2-3_p131_PiwienPilipuk2023-10-03T14:12:06Z Correlation between pregnanesteroid conformation, receptor affinity, and anti-natriuretic effect Piwien-Pilipuk, G. Kanelakis, K.C. Galigniana, M.D. 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 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. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00142999_v454_n2-3_p131_PiwienPilipuk |
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Universidad de Buenos Aires |
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I-28 |
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R-134 |
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Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
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 |
| spellingShingle |
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 Piwien-Pilipuk, G. Kanelakis, K.C. Galigniana, M.D. Correlation between pregnanesteroid conformation, receptor affinity, and anti-natriuretic effect |
| topic_facet |
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 |
| description |
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. |
| format |
JOUR |
| author |
Piwien-Pilipuk, G. Kanelakis, K.C. Galigniana, M.D. |
| author_facet |
Piwien-Pilipuk, G. Kanelakis, K.C. Galigniana, M.D. |
| author_sort |
Piwien-Pilipuk, G. |
| title |
Correlation between pregnanesteroid conformation, receptor affinity, and anti-natriuretic effect |
| title_short |
Correlation between pregnanesteroid conformation, receptor affinity, and anti-natriuretic effect |
| title_full |
Correlation between pregnanesteroid conformation, receptor affinity, and anti-natriuretic effect |
| title_fullStr |
Correlation between pregnanesteroid conformation, receptor affinity, and anti-natriuretic effect |
| title_full_unstemmed |
Correlation between pregnanesteroid conformation, receptor affinity, and anti-natriuretic effect |
| title_sort |
correlation between pregnanesteroid conformation, receptor affinity, and anti-natriuretic effect |
| url |
http://hdl.handle.net/20.500.12110/paper_00142999_v454_n2-3_p131_PiwienPilipuk |
| work_keys_str_mv |
AT piwienpilipukg correlationbetweenpregnanesteroidconformationreceptoraffinityandantinatriureticeffect AT kanelakiskc correlationbetweenpregnanesteroidconformationreceptoraffinityandantinatriureticeffect AT galignianamd correlationbetweenpregnanesteroidconformationreceptoraffinityandantinatriureticeffect |
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1807322329472040960 |