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Serotonin‐induced vascular contractions are regulated by rhoA localization within caveolar microdomains
Author(s) -
Lamping Kathryn G,
England Sarah K,
Nuno Daniel W
Publication year - 2010
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.24.1_supplement.820.3
Subject(s) - rhoa , caveolae , microbiology and biotechnology , rho associated protein kinase , serotonin , chemistry , biophysics , kinase , biology , signal transduction , biochemistry , receptor
RhoA is compartmentalized within caveolae in vascular tissue to regulate activation. We hypothesized that in the absence of caveolin‐1 (cav‐1), a requirement for caveolar formation, localization of rhoA is disrupted increasing activation of rhoA and its downstream effector, rho kinase (ROCK) and enhancing ROCK‐dependent contractions. These studies compared targeting of rhoA and ROCK to caveolar microdomains in aorta from wild‐type (WT) and cav‐1 deficient mice (cav‐1 KO) before and after contraction to serotonin (1 uM). In WT, rhoA and ROCK were primarily localized in high‐density sucrose gradient fractions. Following serotonin, rhoA and ROCK expression increased in low‐density cav‐1 containing fractions. In the absence of cav‐1, rhoA and ROCK no longer compartmentalized in aortic membranes in the presence or absence of serotonin. In agreement with these findings, contractions to serotonin were increased in aortic rings from cav‐1 KO mice compared to WT (serotonin 1uM WT 0.70±0.11g; cav‐1 KO 1.02±0.06g, p<0.05). The increased contractions were inhibited by H1152 (1 uM), a specific ROCK inhibitor. We conclude that localization of rhoA in caveolar microdomains impedes its activation and attenuates contractions to rho‐dependent agonists. Disruption of rhoA localization within microdomains may lead to increased activation in cardiovascular disease. (Support: Dept Veterans Affairs and HD37831)