Abstract
We investigated whether elevations of intracellular cyclic nucleotides (cAMP and cGMP) or elevation of intracellular Ca2+([Ca2+]i) inhibits cell proliferation and migration of cultured rat vascular smooth muscle cells (A7r5). Cell proliferation activity was measured by incubation of A7r5 cells with WST-1 reagent for 1 hour, followed by measurement of absorbance at 415 nm. Cell migration activity was measured by counting migrated cells through pores of cell culture insert (8-μm size) at 24 hour after feeding cells. Dibutyryl cAMP (db-cAMP, 0.03 to 3.0 mM) significantly inhibited cell proliferation in a dose-dependent manner, whereas db-cGMP (0.03 to 3.0 mM) had no effect. Olprinone hydrochloride (OPN, type 3 phosphodiesterase inhibitor) inhibited cell proliferation and enhanced db-cAMP (0.3 mM)-induced inhibition of cell proliferation. Elevation of [Ca2+]i by KCl (70 to 80 mM) and Bay K 8644 (above 30 μM) significantly inhibited cell proliferation. Low concentrations of Bay K 8644 (3 to 30 μM) stimulated cell proliferation. Nifedipine (1 to 100 μM) inhibited dose-dependently cell proliferation. Cell migration activity was significantly inhibited by db-cAMP (3 mM), but not by db-cAMP (0.3 mM) nor by OPN (1 mM). Db-cAMP (0.3 mM) plus OPN (1 mM), however, significantly inhibited cell migration activity. Thus, elvation of cAMP inhibits cell proliferation and cell migration of VSM cells and elevation of [Ca2+]i may have biphasic effect on cell proliferation. [J Physiol Sci. 2007;57 Suppl:S133]
