EFFECTS OF SOMATOSTATIN ON CULTURED HUMAN MESANGIAL CELLS

The present experiments were devoted to analyzing the hypothesis that somatostatin (SS) could modulate glomerular filtration rate by interac ting with mesangial cells. Studies were performed in cultured human me sangial cells, passages 3-5. Radioligand experiments demonstrated the presence in the cells of two kinds of receptors, with high (dissociati on constant 14 pM. Number of sites: 426 fmol/mg) and low (dissociation constant 56 pM. Number of sites: 20, 111 fmol/mg) affinity. SS preven ted in a dose-dependent manner the reduction in planar cell surface ar ea induced by 100 mM Angiotensin II (AII). This effect was not inhibit ed by the blockade of the vasorelaxing prostaglandins (indomethacin, 1 0 mu M), nitric oxide (L-N-methyl-arginine, 0.2 mM), adenylate cyclase (2,5'-dideoxyadenosine, 0.1 mM), or guanylate cyclase (Methylene blue , 30 mu M; LY-83583, 10 mu M), but it was potentiated by zaprinast, an inhibitor of the cyclic GMP (cGMP)-specific phosphodiesterase. SS als o blocked the increase in myosin Light chain phosphorylation induced b y AII. SS increased cGMP synthesis by cultured human mesangial cells, an effect that seemed to be dependent on the stimulation of a particul ate guanylate cyclase. Pre-incubation of the cells with pertussis toxi n (0.5 mu g/ml) inhibited the effect of SS on the AII-dependent change s in planar cell surface area, as well as the SS-dependent cGMP stimul ation. In summary, these results demonstrate the ability of SS to rela x cultured human mesangial cells, thus supporting a role for this pept ide in the regulation of the glomerular filtration rate. The SS-depend ent mesangial cell relaxation may be due to changes in the intracellul ar concentrations of cGMP, as a consequence of the activation of a par ticulate guanylate cyclase.