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Dissociation of natriuresis and diuresis by oxytocin molecular forms in rats

In the rat, oxytocin (OT) produces dose-dependent diuretic and natriuretic responses. Post-translational enzymatic conversion of the OT biosynthetic precursor forms both mature and C-terminally extended peptides. The plasma concentrations of these C-terminally extended peptides (OT-G; OT-GK and OT-G...

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Autores principales: Jankowski, Marek, Danalache, Bogdan A., Plante, Eric, Menaouar, Ahmed, Florian, Maria, Tan, Ju Jing, Grygorczyk, Ryszard, Broderick, Tom L., Gutkowska, Jolanta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6608960/
https://www.ncbi.nlm.nih.gov/pubmed/31269062
http://dx.doi.org/10.1371/journal.pone.0219205
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author Jankowski, Marek
Danalache, Bogdan A.
Plante, Eric
Menaouar, Ahmed
Florian, Maria
Tan, Ju Jing
Grygorczyk, Ryszard
Broderick, Tom L.
Gutkowska, Jolanta
author_facet Jankowski, Marek
Danalache, Bogdan A.
Plante, Eric
Menaouar, Ahmed
Florian, Maria
Tan, Ju Jing
Grygorczyk, Ryszard
Broderick, Tom L.
Gutkowska, Jolanta
author_sort Jankowski, Marek
collection PubMed
description In the rat, oxytocin (OT) produces dose-dependent diuretic and natriuretic responses. Post-translational enzymatic conversion of the OT biosynthetic precursor forms both mature and C-terminally extended peptides. The plasma concentrations of these C-terminally extended peptides (OT-G; OT-GK and OT-GKR) are elevated in newborns and pregnant rats. Intravenous injection of OT-GKR to rats inhibits diuresis, whereas injection of amidated OT stimulates diuresis. Since OT and OT-GKR show different effects on the urine flow, we investigated whether OT-GKR modulates renal action by inhibition of the arginine-vasopressin (AVP) receptor V(2) (V(2)R), the receptor involved in renal water reabsorption. Experiments were carried out in the 8-week-old Wistar rats receiving intravenous (iv) injections of vehicle, OT, OT-GKR or OT+OT-GKR combination. OT (10 μmol/kg) increased urine outflow by 40% (P<0.01) and sodium excretion by 47% (P<0.01). Treatment with OT-GKR (10 μmol/kg) decreased diuresis by 50% (P<0.001), decreased sodium excretion by 50% (P<0.05) and lowered potassium by 42% (P<0.05). OT antagonist (OTA) reduced diuresis and natriuresis exerted by OT, whereas the anti-diuretic effect of OT-GKR was unaffected by OTA. The treatment with V(2)R antagonist (V(2)A) in the presence and absence of OT induced diuresis, sodium and potassium outflow. V(2)A in the presence of OT-GKR only partially increased diuresis and natriuresis. Autoradiography and molecular docking analysis showed potent binding of OT-GKR to V(2)R. Finally, the release of cAMP from CHO cells overexpressing V(2) receptor was induced by low concentration of AVP (EC50:4.2e-011), at higher concentrations of OT (EC50:3.2e-010) and by the highest concentrations of OT-GKR (EC50:1.1e-006). OT-GKR potentiated cAMP release when combined with AVP, but blocked cAMP release when combined with OT. These results suggest that OT-GKR by competing for the OT renal receptor (OTR) and binding to V(2)R in the kidney, induces anti-diuretic, anti-natriuretic, and anti-kaliuretic effects.
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spelling pubmed-66089602019-07-12 Dissociation of natriuresis and diuresis by oxytocin molecular forms in rats Jankowski, Marek Danalache, Bogdan A. Plante, Eric Menaouar, Ahmed Florian, Maria Tan, Ju Jing Grygorczyk, Ryszard Broderick, Tom L. Gutkowska, Jolanta PLoS One Research Article In the rat, oxytocin (OT) produces dose-dependent diuretic and natriuretic responses. Post-translational enzymatic conversion of the OT biosynthetic precursor forms both mature and C-terminally extended peptides. The plasma concentrations of these C-terminally extended peptides (OT-G; OT-GK and OT-GKR) are elevated in newborns and pregnant rats. Intravenous injection of OT-GKR to rats inhibits diuresis, whereas injection of amidated OT stimulates diuresis. Since OT and OT-GKR show different effects on the urine flow, we investigated whether OT-GKR modulates renal action by inhibition of the arginine-vasopressin (AVP) receptor V(2) (V(2)R), the receptor involved in renal water reabsorption. Experiments were carried out in the 8-week-old Wistar rats receiving intravenous (iv) injections of vehicle, OT, OT-GKR or OT+OT-GKR combination. OT (10 μmol/kg) increased urine outflow by 40% (P<0.01) and sodium excretion by 47% (P<0.01). Treatment with OT-GKR (10 μmol/kg) decreased diuresis by 50% (P<0.001), decreased sodium excretion by 50% (P<0.05) and lowered potassium by 42% (P<0.05). OT antagonist (OTA) reduced diuresis and natriuresis exerted by OT, whereas the anti-diuretic effect of OT-GKR was unaffected by OTA. The treatment with V(2)R antagonist (V(2)A) in the presence and absence of OT induced diuresis, sodium and potassium outflow. V(2)A in the presence of OT-GKR only partially increased diuresis and natriuresis. Autoradiography and molecular docking analysis showed potent binding of OT-GKR to V(2)R. Finally, the release of cAMP from CHO cells overexpressing V(2) receptor was induced by low concentration of AVP (EC50:4.2e-011), at higher concentrations of OT (EC50:3.2e-010) and by the highest concentrations of OT-GKR (EC50:1.1e-006). OT-GKR potentiated cAMP release when combined with AVP, but blocked cAMP release when combined with OT. These results suggest that OT-GKR by competing for the OT renal receptor (OTR) and binding to V(2)R in the kidney, induces anti-diuretic, anti-natriuretic, and anti-kaliuretic effects. Public Library of Science 2019-07-03 /pmc/articles/PMC6608960/ /pubmed/31269062 http://dx.doi.org/10.1371/journal.pone.0219205 Text en © 2019 Jankowski et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Jankowski, Marek
Danalache, Bogdan A.
Plante, Eric
Menaouar, Ahmed
Florian, Maria
Tan, Ju Jing
Grygorczyk, Ryszard
Broderick, Tom L.
Gutkowska, Jolanta
Dissociation of natriuresis and diuresis by oxytocin molecular forms in rats
title Dissociation of natriuresis and diuresis by oxytocin molecular forms in rats
title_full Dissociation of natriuresis and diuresis by oxytocin molecular forms in rats
title_fullStr Dissociation of natriuresis and diuresis by oxytocin molecular forms in rats
title_full_unstemmed Dissociation of natriuresis and diuresis by oxytocin molecular forms in rats
title_short Dissociation of natriuresis and diuresis by oxytocin molecular forms in rats
title_sort dissociation of natriuresis and diuresis by oxytocin molecular forms in rats
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6608960/
https://www.ncbi.nlm.nih.gov/pubmed/31269062
http://dx.doi.org/10.1371/journal.pone.0219205
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