Downregulation of caveolin expression by cAMP signal

Recent data have demonstrated that caveolin, a major structural protein of caveolae, inhibits the function of molecules involved in cAMP signaling suc h as adenylyl cyclase. We examined the effect of cAMP signal on the express ions of caveolin subtypes using rat cardiac myoblasts (H9C2 cells) and smoo th muscle cells (RASMC), which express caveolin subtypes. Treatment of RASM C and H9C2 cells with forskolin, an adenylyl cyclase stimulator, decreased caveolin-1 mRNA levels in a dose-dependent manner. Time course studies show ed a time-dependent decrease of caveolin-1 mRNA levels in H9C2 cells (after 6 hours) while caveolin-1 mRNA levels in RASMC showed a biphasic response, i.e., an initial increase (within 3 hours) and a later decrease (after 3 h ours). Similar biphasic changes were observed when RASMC was treated with I BMX, a phosphodiesterase inhibitor. The levels of caveolin-1 and -3 protein s were also decreased by forskolin treatment, but only after 60-72 hours in RASMC and 24-36 hours in H9C2 cells. In contrast, the expression of caveol in-2 remained similar in both cells and decreased to a small degree after p rolonged treatment. Therefore, the expression of caveolin is downregulated by cAMP signal in a caveolin subtype-dependent manner.