AJP - Renal Physiology, Vol 259, Issue 3 425-F431, Copyright © 1990 by American Physiological Society
Inhibitory effect of phorbol ester on sodium transport in frog urinary bladder
T. Satoh and H. Endou
Department of Pharmacology, Faculty of Medicine, University of Tokyo, Japan.
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.
