Angiotensin II stimulates phosphoinositide turnover and phosphorylase through AII-1 receptors in isolated rat hepatocytes.
Angiotensin II stimulated the activity of phosphorylase a (EC50 approximately 3 nM). The effect of two receptor subtype-selective nonpeptide antagonists, DuP 753 (AII-1 selective) and PD123177 (AII-2 selective), was studied. It was observed that DuP 753 inhibited the effect of angiotensin II (IC50 100 nM) but in contrast, PD123177 was without effect on this action of the peptide hormone. Angiotensin II stimulated the labeling of phosphatidylinositol (resynthesis) and the release of inositol phosphates (breakdown). These effects of angiotensin II were blocked by DuP 753 but not by PD123177. The antagonists were without effect by themselves on these parameters. The results clearly indicate that angiotensin II receptors of the AII-1 subtype are coupled to phosphoinositide turnover and mediate phosphorylase activation in isolated rat hepatocytes.
García-Sáinz
J A
JA
Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México.
Macías-Silva
M
M
D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D002478:Cells, Cultured; D005260:Female; D007093:Imidazoles / Q000494:pharmacology; D007295:Inositol Phosphates / Q000378:metabolism*; D007700:Kinetics; D019808:Losartan; D010716:Phosphatidylinositols / Q000378:metabolism*; D010762:Phosphorylase a / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011945:Receptors, Angiotensin / Q000187:drug effects / Q000378:metabolism*; D013777:Tetrazoles / Q000494:pharmacology
D000959:Antihypertensive Agents; D007093:Imidazoles; D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D011725:Pyridines; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; C066253:PD 123177; D010762:Phosphorylase a; D019808:Losartan