Inhibitory effect of phorbol ester on sodium transport in frog urinary bladder.
To confirm the role of protein kinase C (PKC) on epithelial Na transport, we studied the effects of phorbol 12-myristate 13-acetate (PMA) and dioctanoylglycerol (DiC8), activators of PKC, on short-circuit current (Isc) in frog urinary bladder and further examined the influence of sphingosine, an inhibitor of PKC, on PMA- or DiC8-modulated Isc. PMA reduced basal Isc in a dose-dependent manner, and sphingosine (10 and 100 microM) partially restored PMA-reduced Isc. On the other hand, DiC8 (5 x 10(-5) M) also reduced basal Isc, and this action was completely prevented by 100 microM sphingosine. Both PMA (4 x 10(-5) M) and DiC8 inhibited vasopressin (50 mU/ml)- and forskolin (5 x 10(-5) M)-stimulated increases in Isc. PMA (4 x 10(-5) M) also inhibited 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP)-stimulated increase in Isc. Furthermore, PMA (4 x 10(-5) M) and DiC8 (5 x 10(-5) M) inhibited vasopressin (50 mU/ml)-stimulated cAMP accumulation. DiC8 also inhibited forskolin-stimulated cAMP accumulation. These results indicate that PMA exerts inhibitory influence on Na transport mainly by its own potency of PKC activation. In addition, it is suggested that there is a cross talk in epithelial Na transport between PKC and cAMP-dependent pathway in frog urinary bladder.
Satoh
T
T
Department of Pharmacology, Faculty of Medicine, University of Tokyo, Japan.
Endou
H
H
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004075:Diglycerides / Q000494:pharmacology; D011892:Rana catesbeiana; D012964:Sodium / Q000378:metabolism*; D013110:Sphingosine / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D001743:Urinary Bladder / Q000378:metabolism*
D004075:Diglycerides; C044295:1,2-dioctanoylglycerol; D001127:Arginine Vasopressin; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D012964:Sodium; D000242:Cyclic AMP; D013110:Sphingosine; D013755:Tetradecanoylphorbol Acetate