Role for protein kinase C in the modulation of glomerular PGE2 production by angiotensin II.
Angiotensin II increased PGE2 release from superfused glomeruli, and stimulated labeled inositol phosphate production. 12-O-Tetradecanoyl phorbol -13-acetate (TPA, 10(-7) M), which stimulates protein kinase C activity in soluble fractions of glomerular homogenates, suppressed angiotensin II actions on inositol phosphate production and PGE2. By contrast, 4a phorbol 12,13 di-decanoate and phorbol had no effect on protein kinase C activity or angiotensin II induced increases in inositol phosphate or PGE2. 1-(5-Isoquinolinyl)-2-methylpiperazine (H-7), which inhibits protein kinase C activity in soluble fractions of glomerular homogenates, prevented TPA induced suppression of angiotensin II actions on inositol phosphate production and PGE2. Moreover H-7 prolonged the time course of angiotensin II induced inositol phosphate production and enhanced angiotensin II actions on glomerular PGE2 production. The results support a role for inositol phospholipid hydrolysis through the phospholipase C pathway in the mediation of angiotensin II actions on PGE2 in glomeruli and are consistent with negative modulation of these actions by protein kinase C.
Craven
P A
PA
Department of Medicine, VA Medical Center, Pittsburgh, PA 15240.
Patterson
M C
MC
DeRubertis
F R
FR
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D015232:Dinoprostone; D005260:Female; D007546:Isoquinolines / Q000494:pharmacology; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism*; D010703:Phorbol Esters / Q000494:pharmacology; D010704:Phorbols / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011458:Prostaglandins E / Q000096:biosynthesis*; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D007546:Isoquinolines; D010703:Phorbol Esters; D010704:Phorbols; D010879:Piperazines; D011458:Prostaglandins E; D000804:Angiotensin II; C008876:phorbol-12,13-didecanoate; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate; C033085:phorbol