MODULATION OF THE VASCULAR SMOOTH-MUSCLE ANGIOTENSIN SUBTYPE 2 (AT(2)) RECEPTOR BY ANGIOTENSIN-II

The angiotensin subtype 2 (AT(2)) receptor is scarce in most adult vas cular tissues except after injury. Since angiotensin II (AngII) is rel eased upon injury, we examined the possibility that AngII governs AT(2 ) receptor expression in smooth muscle cells (SMC). A polyclonal antis erum, raised to a peptide corresponding to the AT(2) receptor C-termin us, recognized a similar to 45-kDa protein after transfection of cos-7 cells with AT(2) receptor cDNA Detection of a similar to 65-kDa band in extracts of SMC indicated that the AT(2) receptor was glycosylated. Treatment of SMCs with AngII increased AT(2) receptor levels fourfold over 24 h. This response was abrogated by losartan, but not by PD1233 19, indicating AT(1) receptor involvement. AngII-dependent increases i n AT(2) receptor levels were also prevented by LY294002, an inhibitor of phosphatidyinositol 3-kinase, but not by rapamycin. These results i ndicate AngII influences AT(2) receptor expression through the AT(1) r eceptor via a signaling pathway that includes PI3K. (C) 1998 Academic Press.