ANGIOTENSIN-II RECEPTOR SUBTYPES PLAY OPPOSITE ROLES IN REGULATING PHOSPHATIDYLINOSITOL HYDROLYSIS IN RAT SKIN SLICES

Among the many functions of angiotensin II (Ang II) it now appears that Ang II is a growth factor. The concentration of Ang II in rat skin has been shown to increase during wound healing. To investigate the intracellular effect of Ang II in skin we determined the levels of total cytoplasmic inositol phosphates after incubation of skin slices with different doses of Ang II. 10-6 M of Ang II increased significantly the phosphatidylinositol (PI) hydrolysis, and the effect was dose dependent up to 10-4 M Ang II. The majority of inositol phosphates yielded after 1 hour incubation in the presence of lithium was InsP2 with lesser amount of InsP2. Losartan, the Ang II AT1 antagonist, at a dose of 10-4M blocked the effect of Ang II, while PD123319, the Ang II AT2 antagonist, had no antagonistic action; PD123319 at the higher dose of 10-3 M, however, potentiated the effect of Ang II on PI hydrolysis. The results suggest that PI hydrolysis is a second messenger system for Ang II in rat skin. Also, the two subtypes of Ang II receptors mediate opposite effects on PI hydrolysis: Ang II binding to AT, receptors increases inositol phosphate production, while Ang II binding to AT2 receptors decreases inositol phosphate production. © 1992 Academic Press, Inc.