Phorbol myristate acetate and dioctanoylglycerol inhibit transport in rabbit proximal convoluted tubule

Abstract

The present in vitro microperfusion study examined the effect of protein kinase C activation on transport in the rabbit proximal convoluted tubule (PCT). PCT were perfused with an ultrafiltrate-like solution and were bathed in a serumlike albumin solution. Addition of 5 x 10(-8) and 5 x 10(-7) M bath phorbol 12-myristate 13-acetate, an activator of protein kinase C, inhibited volume absorption from 1.06 +/- 0.10 to 0.77 +/- 0.07 nl.mm-1.min-1 (P less than 0.05) and 0.76 +/- 0.14 to 0.48 +/- 0.08 nl.mm-1.min-1 (P less than 0.01), respectively. Bath phorbol 12-myristate 13-acetate (5 x 10(-9) M) had no effect on volume absorption (Jv, 0.82 +/- 0.13 to 0.81 +/- 0.12 nl.mm-1.min-1). In contrast, 5 x 10(-8) M bath 4 alpha-phorbol, an inactive phorbol that does not activate protein kinase C, had no effect on Jv (0.95 +/- 0.14 to 0.94 +/- 0.11 nl.mm-1.min-1). Bath L-alpha-dioctanoylglycerol (10(-4) M), another known activator of protein kinase C, inhibited volume absorption from 0.96 +/- 0.08 to 0.71 +/- 0.08 nl.mm-1.min-1 (P less than 0.001). A 10-fold lower concentration of L-alpha-dioctanoylglycerol (10(-5) M) had no effect on Jv (0.81 +/- 0.18 to 0.78 +/- 0.17 nl.mm-1.min-1). Both 5 x 10(-8) M phorbol 12-myristate 13-acetate and 10(-4) M L-alpha-dioctanoylglycerol inhibited glucose, bicarbonate, and chloride transport in the PCT. These data are consistent with protein kinase C activation playing a role in the modulation of proximal tubular transport.