Modulation of the vascular smooth muscle angiotensin subtype 2 (AT2) receptor by angiotensin II.
The angiotensin subtype 2 (AT2) receptor is scarce in most adult vascular tissues except after injury. Since angiotensin II (AngII) is released upon injury, we examined the possibility that AngII governs AT2 receptor expression in smooth muscle cells (SMC). A polyclonal antiserum, raised to a peptide corresponding to the AT2 receptor C-terminus, recognized a approximately 45-kDa protein after transfection of cos-7 cells with AT2 receptor cDNA. Detection of a approximately 65-kDa band in extracts of SMC indicated that the AT2 receptor was glycosylated. Treatment of SMCs with AngII increased AT2 receptor levels fourfold over 24 h. This response was abrogated by losartan, but not by PD123319, indicating AT1 receptor involvement. AngII-dependent increases in AT2 receptor levels were also prevented by LY294002, an inhibitor of phosphatidyinositol 3-kinase, but not by rapamycin. These results indicate AngII influences AT2 receptor expression through the AT1 receptor via a signaling pathway that includes PI3K.
Zahradka
P
P
Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, Manitoba, Canada.
Yau
L
L
Lalonde
C
C
Buchko
J
J
Thomas
S
S
Werner
J
J
Nguyen
M
M
Saward
L
L
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D000918:Antibody Specificity; D019556:COS Cells; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000235:genetics; D006031:Glycosylation; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D011817:Rabbits; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D013552:Swine; D014162:Transfection
D018076:DNA, Complementary; D007093:Imidazoles; D011725:Pyridines; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D000804:Angiotensin II; C073402:PD 123319; D019869:Phosphatidylinositol 3-Kinases; D019808:Losartan