AT1 and AT2 receptors in human glomerular endothelial cells at different passages.
In human adult kidney angiotensin II (AngII) effects are mediated by the AT1 receptor, while the functions of AT2 receptors are mostly unknown. Since AngII regulates endothelial cell growth by AT1 and AT2 receptors, we analysed their functional aspects at different passages in human glomerular endothelial cells (GENC). Semiquantitative reverse transcription-polymerase chain reaction revealed the presence of AT1 and AT2 receptors between 2p and 15p cell passages with different levels of expression. In fact, binding studies of different families of displacement curves using AngII, DUP753 (AT1 antagonist), and PD123177 (AT2 antagonist) showed the presence of AT1a and AT2 receptors at 4p-9p while in GENC 2p only the presence of AT2. In terms of mitogenic activity, AngII was unable to stimulate GENC 2p growth. On the contrary, in GENC 4p-9p and 15p a significant thymidine incorporation was observed. This stimulatory effect seemed to be induced also by the concomitant release of PDGF-BB AT1a mediated. In conclusion, AT1a and AT2 receptors are represented in GENC with a different ratio depending upon the cell passage. AngII regulates the mitogenic effect through AT1a receptors (in later cell passages 4p-15p) involving the release of PDGF-BB, while AT2 (in early cell passage 2p) showed a predominant negative growth control.
Cresci
Barbara
B
Department of Clinical Pathophysiology, Endocrinology Unit, Diabetes and Metabolic Diseases Section, University of Florence, Viale Pieraccini 6-50134, Florence, Italy.
Giannini
Stefano
S
Pala
Laura
L
Mavilia
Carmelo
C
Manuelli
Cinzia
C
Cappugi
Pietro
P
Maggi
Enrico
E
Rotella
Carlo M
CM
Magg
Enrico
E
D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers; D057912:Angiotensin II Type 2 Receptor Blockers; D000959:Antihypertensive Agents / Q000494:pharmacology; D015153:Blotting, Western; D018929:Cell Culture Techniques / Q000379:methods*; D002455:Cell Division; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000378:metabolism*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007678:Kidney Glomerulus / Q000378:metabolism*; D007700:Kinetics; D019808:Losartan / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D011485:Protein Binding; D011725:Pyridines / Q000494:pharmacology; D044140:Receptor, Angiotensin, Type 1 / Q000096:biosynthesis*; D044139:Receptor, Angiotensin, Type 2 / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors
D047228:Angiotensin II Type 1 Receptor Blockers; D057912:Angiotensin II Type 2 Receptor Blockers; D000959:Antihypertensive Agents; D007093:Imidazoles; D010982:Platelet-Derived Growth Factor; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II; C066253:PD 123177; D019808:Losartan; D013936:Thymidine