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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...

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Detalles Bibliográficos
Autores principales: Bai, Juan, Duraisamy, Karthi, Mak, Sarah O. K., Allam, Ahmed, Ajarem, Jamaan, Li, Zhang, Chow, Billy K. C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6719825/
https://www.ncbi.nlm.nih.gov/pubmed/31479491
http://dx.doi.org/10.1371/journal.pone.0222005
Descripción
Sumario: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 ([Ca(2+)](i)) when exposed to ANGII but not from the SCTR(-/-) ZG cells. Synthetic SCTR transmembrane (TM) peptides STM-II/-IV were able to alter [Ca(2+)](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 [Ca(2+)](i).