HYPERGRAVITY MODULATES CYCLIC GMP EFFLUX IN NITRIC OXIDE-STIMULATED HUMAN MELANOCYTIC CELLS

摘要

Gravity alteration is known to influence cell functions. We recently found that hypergravity may stimulate cGMP efflux in human melanocytic cells when cGMP hydrolysis is inhibited. Here we examined whether hypergravity modulates cGMP efflux in nitric oxide (NO)-stimulated melanocytes and melanoma cells (MCs) using NONOates as direct NO donors. In the presence of 0.1 mM DETA-NO and long-term application of hypergravity (up to 5g for 24 h) an elevated cGMP efflux in cultured melanocytes and non-metastatic MCs compared to 1g was observed, whereas short-term exposure was not effective. The hypergravity-stimulated cGMP efflux was inhibited by 1μM trequinsin, a selective inhibitor of the multidrug resistance proteins 4 and 5 (MRP4/5). The results of the present study indicate that hypergravity may stimulate cGMP efflux in NO-stimulated human melanocytes and non-metastatic MCs most probably by an enhanced expression of MRP4/5. Thus, an altered acceleration vector may induce signaling events in human melanocytic cells.