‘Modulation of ANF-RZ/ANP-C Rccv+ors by Angiotensin II in Vascular Smoot ii Muscle Cells

In !he present studies, we have investigated the modulation of atria1 nalriuretic factor (ANF) receptor of 82 subtype (ANF-RZ) coupled to adenylyl cyclase!cAMP Fignal transduction system by angiotensir 11 (All). C-ANFIm2, I CANFI-z~,IdesfGln’R, Ser’“, Gin=, Leu”, GlyzZ)ANF,-,,-NH21 and A!1 inhibited adenylyl cyclase activity in control vascular smooth muscle cells (VSMC A-10) by about 40% and 30% respectively. Pretreatment of the cells with All resulted in the attenuation of both C-ANF$. 2,and AII-mediated inhibition of adenylyl cyrlase. Losartan treatment of the cells was able to partially block (-SO%..) the .41Ias well as CANF,-,-mediated inhibitions of adenylyl cyclase that are completely lost by All pretreatment. The pretreatment of the cells with All alone or with losartan did not affect the [“‘II-ANF binding to ANF reczptsrs. However, All treatment resulted in the augmentation of the levels of Girr2 and Gia3. On the other hand, staurosporine (a protein kinase C iPltCl Inhibitor) treatment of cells before All treatment was able to prevent the attenuation of both C-ANF,.?, as well as AIImediated inhibition of adenylyl cyclase elicited by All. These results indicate that the AI1 modulation of ANF-R2 receptor-mediated inhibition of adenylyl cycIase is independent of ANF-R2 receptor density or the 1~~1s of Gi regulatory protein and may be due to the uncoupling of the ANF-R2 receptor from the Ci protein. This uncoupling may be associated with the phosphorylatinn of the Gi protein by PKC activated by All. Am J Hypertens 1996;9:930-934