Inhibition by phorbol ester of cellular adenosine 3',5'-monophosphate production and cellular free calcium mobilization in response to arginine vasopressin in rat renal papillary collecting tubule cells in culture.
We determined whether tumor-promoting factor phorbol ester modulates cellular cAMP production and the cellular free calcium concentration ([Ca2+]i) in response to arginine vasopressin (AVP) in rat renal papillary collecting tubule cells in culture. In the presence of 5 x 10(-4) M 3-isobutyl-1-methylxanthine, AVP increased cellular cAMP production in a dose-dependent manner. A 1-h exposure to 3 x 10(-7)-3 x 10(-6) M phorbol-12-myristate-13-acetate (PMA) significantly attenuated the cAMP response to AVP (1 x 10(-9) M AVP; 474.9 +/- 24.8 vs. 368.1 +/- 22.8 fmol/microgram protein; P less than 0.01). The dose-response relation with AVP thus shifted to the right. Such an inhibition was totally reversed in the presence of 2 x 10(-6) M 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7), an inhibitor of protein kinase-C. Also, 1 x 10(-7) M AVP produced an increase in [Ca2+]i from 99.4 +/- 3.3 to 200.0 +/- 8.6 nM. When cells were preexposed to 1 x 10(-6) M PMA, an increase in [Ca2+]i in response to 1 x 10(-7) M AVP was significantly diminished (75.5 +/- 4.6 to 101.4 +/- 4.3 nM). The inhibition by PMA of AVP-induced increment in [Ca2+]i was significantly attenuated in the presence of 2 x 10(-5) M H-7 compared to that in its absence. Prolonged exposure to PMA did not alter the AVP-induced increases in cAMP production and [Ca2+]i. These results indicate that phorbol ester inhibits the cellular action of AVP mediated through the activation of protein kinase-C and suggest that there is an interaction between cAMP and phosphatidylinositol systems in modulating the AVP action in renal papillary collecting tubule cells.
Ishikawa
S
S
Department of Medicine, Jichi Medical School, Tochigi, Japan.
Saito
T
T
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007546:Isoquinolines / Q000494:pharmacology; D007679:Kidney Medulla; D007685:Kidney Tubules, Collecting / Q000166:cytology / Q000378:metabolism*; D008297:Male; D009994:Osmolar Concentration; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013997:Time Factors
D007546:Isoquinolines; D010879:Piperazines; D001127:Arginine Vasopressin; D005576:Colforsin; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000242:Cyclic AMP; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium