Annexin ii inhibition of g protein-regulated inositol trisphosphate formation in rat aortic smooth muscle cells. Schelling, Jeffrey R., Douglas J. Gentry, and George R. Dubyak. Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH 44106, Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, OH 44106
APStracts 2:0175F, 1995.
Vasoconstrictor hormones contribute to the pathogenesis of hypertension through intracellular signals which stimulate vascular smooth muscle (VSMC) contraction and/or growth. We have previously shown that the glucocorticoid dexamethasone (DEX) inhibited angiotensin II-stimulated inositol trisphosphate (IP3) formation in VSMC, but the mechanism of inhibition is not known. Since glucocorticoids stimulate the expression of annexins, and annexin II potently binds phosphoinositides, the role of DEX and annexin II in VSMC G protein-coupled phosphoinositide hydrolysis was investigated. DEX incubation blunted increases in GTP[gamma]S-stimulated IP3 generation and angiotensin II-induced Ca2+i mobilization, but stimulated elevations in VSMC annexin II content. VSMC incubation with exogenous, purified annexin II resulted in concentration -dependent decreases in GTP[gamma]S-stimulated IP3 formation. In DEX -treated cells, exogenous annexin II did not further diminish GTP[gamma]S-stimulated IP3 formation, suggesting that endogenous annexin II may be a mediator of DEX-induced inhibition of G protein -coupled IP3 generation. These data represent the first direct evidence of G protein-dependent phosphoinositide hydrolysis regulation by glucocorticoids or annexins. We speculate that annexin II may play a role in the pathogenesis of hypertension through stimulation of VSMC growth. 

Received 21 April 1995; accepted in final form 19 September 1995.
APS Manuscript Number F129-5.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 November 95