Phorbol myristate acetate and dioctanoylglycerol inhibit transport in rabbit proximal convoluted tubule
Baum, M.; Hays, S.R.
American Journal of Physiology 254(1 Pt 2): F9-14
1988
ISSN/ISBN: 0002-9513 PMID: 2827521 Document Number: 311458
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 .times. 10-8 and 5 .times. 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 .cntdot. mm-1 .cntdot. min-1 (P < 0.05) and 0.76 .+-. 1.14 to 1.48 .+-. 0.08 nl .cntdot. mm-1 .cntdot. min-1 (P < 0.01), respectively. Bath phorbol 12-myristate 13-acetate (5 .times. 10-9 M) had no effect on volume absorption (Jv, 0.82 .+-. 0.13 to 0.81 .+-. 0.12 nl .cntdot. mm-1 .cntdot. min-1). In contrast, 5 .times. 10-8 M bath 4.alpha.-phorbol, an inactive phorbol that does not acitvate protein kinase C, had no effect on Jv (0.95 .+-. 0.14 to 0.94 .+-. 0.11 nl .cntdot. mm-1 .cntdot. 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 .cntdot. mm-1 .cntdot. min-1 (P < 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 .cntdot. mm-1 .cntdot. min-1). Both 5 .times. 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.