SOMATOSTATIN ACTIVATES PARTICULATE GUANYLATE-CYCLASE IN CULTURED RAT MESANGIAL CELLS

Although the ability of somatostatin (ST) to relax cultured rat mesang ial cells has recently been described, the intimate cellular mechanism s responsible for this effect have not been adequately clarified. The present experiments were designed to test the hypothesis that cyclic G MP (cGMP) could be involved in the genesis of this relaxation. ST incr eased cGMP synthesis by cultured rat mesangial cells, in basal conditi ons and in the presence of isobutylmethylxanthine or zaprinast. This e ffect was dose-dependent, with a threshold value of about 1 nM and a m aximal response at ST concentrations between 0.1 and 1 mu M. This incr eased cGMP synthesis was dependent on the stimulation by ST of a parti culate guanylate cyclase, as the synthesis of cGMP by a particulate me mbrane fraction obtained from the cells increased in the presence of S T. When the cGMP-specific phosphodiesterase of mesangial cells was bla cked with zaprinast, the ST-dependent relaxation, assessed both by mor phological and biochemical criteria, significantly increased with resp ect to the experiments performed without zaprinast. These results supp ort a role for cGMP in the ST-dependent relaxation of cultured rat mes angial cells. The increased cGMP synthesis appears to be the consequen ce of the activation of some form of particulate guanylate cyclase.