REGULATION OF P-AMINOHIPPURATE TRANSPORT BY PROTEIN-KINASE-C IN OK KIDNEY EPITHELIAL-CELLS

We studied the effect of phorbol 12-myristate 13-acetate (PMA), a phor bol ester which activates protein kinase C, on p-aminohippurate (PAH) transport in OK cells. PMA (10(-7) M) almost completely inhibited the transcellular transport of PAH across OK cell monolayers from the basa l to the apical side, as well as the accumulation of PAH in the cells. The uptake of PAH across the basolateral membrane of OK cells was inh ibited by PMA in a time- and dose-dependent fashion. Exposing the cell s with other protein kinase C activators such as active phorbol esters and diacylglycerols also resulted in a significant inhibition of baso lateral PAH uptake, but the inactive phorbol ester, 4 alpha-phorbol 12 ,13-didecanoate, had no effect. The inhibition of basolateral PAH upta ke by PMA was blocked by staurosporine, an inhibitor of protein kinase C. Cycloheximide, actinomycin D, colchicine, and cytochalasin D did n ot affect the inhibitory effect of PMA on basolateral PAH uptake. Thes e results suggested that the PAH transport system in OK cells is under the regulatory control of protein kinase C.