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The role of GPR30 in mediating the rapid vascular effects of aldosterone and estrogen
Author(s) -
Gros Robert,
Ding QingMing,
Chorazcyzewski Jozef,
Shaikh Rasha,
Feldman Ross D
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.910.6
Subject(s) - gper , mapk/erk pathway , vascular smooth muscle , endocrinology , medicine , estrogen receptor , contraction (grammar) , phenylephrine , aldosterone , chemistry , estrogen , receptor , biology , signal transduction , microbiology and biotechnology , smooth muscle , cancer , breast cancer , blood pressure
Aldosterone (ALDO) and estrogen (EST) elicit acute vascular effects through rapid signaling pathways. In vascular smooth muscle cells (VSMC), ALDO and EST mediate contraction. However, the mechanisms underlying this common effect remains unclear. Therefore, we examined the role of MR and GPR30 receptors in mediating ALDO and EST rapid effects in VSMC by assessing contractile response using the silicone wrinkling assay and ERK activation by western blotting. Short term (5min) incubations with ALDO or EST (1–1000 nM) mediated dose‐dependent VSMC contraction (ALDO:EC50=43±2 nM; EST:EC50=73±3 nM) and enhanced phenylephrine (PE)‐mediated contraction. The ALDO‐ and EST‐mediated increases in PE‐induced contraction were further enhanced with expression of either MR or GPR30. In contrast to their common effects mediating contraction, short term exposure to ALDO stimulated ERK activation (146 ±7 % of control), whereas EST inhibited ERK activation (67±3% of control), with further inhibition by expression of ERα. However, expression of GPR30 enhanced ALDO mediated‐ERK activation and reversed the effect of estrogen from ERK inhibition to ERK activation (149±11% of control). In summary, these data demonstrate that estrogen and aldosterone‐mediated vascular effects are mediated both by ER and MR, in part, but suggest an important role of GPR30 in mediating VSMC contraction as well as mediating ERK activation in VSMC.