Enhancement of phosphatidylcholine biosynthesis by angiotensin-(1-7) in the rat renal cortex.
In the present paper, we investigated the effect of angiotensin-(1-7) (Ang-(1-7)) on phospholipid biosynthesis in the rat renal cortex. A significant increase in phosphatidylcholine (PC) labeling was observed when cortical slices, prelabeled with [32P]orthophosphate, were incubated for 30 min in the presence of Ang-(1-7) (1 pM to 100 nM). Neither the phospholipase C inhibitors, neomycin or db-cAMP nor the protein kinase C inhibitors, chelerythrine or H7, modified the stimulatory effect induced by 0.1 nM Ang-(1-7). The enhancement of PC biosynthesis caused by 0.1 nM Ang-(1-7) was unmodified by either losartan, an AT(1) receptor antagonist, or (1-[[4-(dimethylamino)-3-methylphenyl]methyl]-5-(diphenylacetyl)-4,5,6,7-tetrahydro-1H-imidazol[4,5-c]pyridine-6-carboxylic acid ditrifluoroacetate) (PD 123319), an AT(2) receptor antagonist, but was partially blocked by [D-Ala(7)]Ang-(1-7), an Ang-(1-7) specific antagonist. However, losartan potentiated the effect of 100 nM Ang-(1-7) on PC biosynthesis. Losartan by itself increased the de novo synthesis of PC. These results suggest that the Ang-(1-7)-mediated increase in PC biosynthesis is independent of AT(1) and AT(2) receptor activation but mediated by a specific Ang-(1-7) receptor. This mechanism is independent of phospholipase C and PKC activation.
Gironacci
Mariela M
MM
Departamento de Química Biológica, Instituto de Química y Fisicoquímica Biológicas, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina.
Fernández-Tomé
María del Carmen
Mdel C
Speziale
Emir
E
Sterin-Speziale
Norma
N
Peña
Clara
C
D000803:Angiotensin I / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D007672:Kidney Cortex / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D010713:Phosphatidylcholines / Q000096:biosynthesis*; D010743:Phospholipids / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology
D057911:Angiotensin Receptor Antagonists; D010446:Peptide Fragments; D010713:Phosphatidylcholines; D010743:Phospholipids; D000803:Angiotensin I; C118790:angiotensin I (1-7)