Role of SCTR/AT1aR heteromer in mediating ANGII-induced aldosterone secretion.
The involvement of secretin (SCT) and its receptor (SCTR) in angiotensin II (ANGII)-mediated osmoregulation by forming SCTR/ angiotensin II type 1 receptor (AT1R) heteromer is well established. In this study, we demonstrated that SCTR/AT1R complex can mediate ANGII-induced aldosterone secretion/rele...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2019-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0222005 |
| _version_ | 1819114048897155072 |
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| author | Juan Bai Karthi Duraisamy Sarah O K Mak Ahmed Allam Jamaan Ajarem Zhang Li Billy K C Chow |
| author_facet | Juan Bai Karthi Duraisamy Sarah O K Mak Ahmed Allam Jamaan Ajarem Zhang Li Billy K C Chow |
| author_sort | Juan Bai |
| collection | DOAJ |
| description | The involvement of secretin (SCT) and its receptor (SCTR) in angiotensin II (ANGII)-mediated osmoregulation by forming SCTR/ angiotensin II type 1 receptor (AT1R) heteromer is well established. In this study, we demonstrated that SCTR/AT1R complex can mediate ANGII-induced aldosterone secretion/release through potentiating calcium mobilization. Through IHC and cAMP studies, we showed the presence of functional SCTR and AT1R in the primary zona glomerulosa (ZG) cells of C57BL/6N (C57), and functional AT1R and non-functional SCTR in SCTR knockout (SCTR-/-) mice. Calcium mobilization studies revealed the important role of SCTR on ANGII-mediated calcium mobilization in adrenal gland. The fluo4-AM loaded primary adrenal ZG cells from the C57 mice displayed a dose-dependent increase in intracellular calcium influx ([Ca2+]i) when exposed to ANGII but not from the SCTR-/- ZG cells. Synthetic SCTR transmembrane (TM) peptides STM-II/-IV were able to alter [Ca2+]i in C57 mice, but not the mice with mutated STM-II/-IV (STM-IIm/IVm) peptides. Through enzyme immunoassay (EIA), we measured the aldosterone release from primary ZG cells of both C57 and SCTR-/- mice by exposing them to ANGII (10nM). SCTR-/- ZG cells showed impaired ANGII-induced aldosterone secretion compared to the C57 mice. TM peptide, STM-II hindered the aldosterone secretion in ZG cells of C57 mice. These findings support the involvement of SCTR/AT1R heterodimer complex in aldosterone secretion/release through [Ca2+]i. |
| first_indexed | 2024-12-22T04:39:07Z |
| format | Article |
| id | doaj.art-62a5f0c6ca3a4e03800e6a98860ec7b5 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T04:39:07Z |
| publishDate | 2019-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-62a5f0c6ca3a4e03800e6a98860ec7b52022-12-21T18:38:47ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-01149e022200510.1371/journal.pone.0222005Role of SCTR/AT1aR heteromer in mediating ANGII-induced aldosterone secretion.Juan BaiKarthi DuraisamySarah O K MakAhmed AllamJamaan AjaremZhang LiBilly K C ChowThe involvement of secretin (SCT) and its receptor (SCTR) in angiotensin II (ANGII)-mediated osmoregulation by forming SCTR/ angiotensin II type 1 receptor (AT1R) heteromer is well established. In this study, we demonstrated that SCTR/AT1R complex can mediate ANGII-induced aldosterone secretion/release through potentiating calcium mobilization. Through IHC and cAMP studies, we showed the presence of functional SCTR and AT1R in the primary zona glomerulosa (ZG) cells of C57BL/6N (C57), and functional AT1R and non-functional SCTR in SCTR knockout (SCTR-/-) mice. Calcium mobilization studies revealed the important role of SCTR on ANGII-mediated calcium mobilization in adrenal gland. The fluo4-AM loaded primary adrenal ZG cells from the C57 mice displayed a dose-dependent increase in intracellular calcium influx ([Ca2+]i) when exposed to ANGII but not from the SCTR-/- ZG cells. Synthetic SCTR transmembrane (TM) peptides STM-II/-IV were able to alter [Ca2+]i in C57 mice, but not the mice with mutated STM-II/-IV (STM-IIm/IVm) peptides. Through enzyme immunoassay (EIA), we measured the aldosterone release from primary ZG cells of both C57 and SCTR-/- mice by exposing them to ANGII (10nM). SCTR-/- ZG cells showed impaired ANGII-induced aldosterone secretion compared to the C57 mice. TM peptide, STM-II hindered the aldosterone secretion in ZG cells of C57 mice. These findings support the involvement of SCTR/AT1R heterodimer complex in aldosterone secretion/release through [Ca2+]i.https://doi.org/10.1371/journal.pone.0222005 |
| spellingShingle | Juan Bai Karthi Duraisamy Sarah O K Mak Ahmed Allam Jamaan Ajarem Zhang Li Billy K C Chow Role of SCTR/AT1aR heteromer in mediating ANGII-induced aldosterone secretion. PLoS ONE |
| title | Role of SCTR/AT1aR heteromer in mediating ANGII-induced aldosterone secretion. |
| title_full | Role of SCTR/AT1aR heteromer in mediating ANGII-induced aldosterone secretion. |
| title_fullStr | Role of SCTR/AT1aR heteromer in mediating ANGII-induced aldosterone secretion. |
| title_full_unstemmed | Role of SCTR/AT1aR heteromer in mediating ANGII-induced aldosterone secretion. |
| title_short | Role of SCTR/AT1aR heteromer in mediating ANGII-induced aldosterone secretion. |
| title_sort | role of sctr at1ar heteromer in mediating angii induced aldosterone secretion |
| url | https://doi.org/10.1371/journal.pone.0222005 |
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