RENAL ORGANIC ANION SECRETION - EVIDENCE FOR DOPAMINERGIC AND ADRENERGIC REGULATION

To examine possible regulatory control of renal proximal tubule organi c anion secretion, winter flounder (Pleuronectes americanus) proximal tubule primary cultures were mounted in Ussing chambers. Unidirectiona l fluxes of [2,4-C-14]dichlorophenoxyacetic acid were determined under short-circuited conditions. Phorbol 12-myristate 13-acetate (1 mu M) caused a significant (P < 0.01) inhibition of net 2,4-dichlorophenoxya cetic acid secretion. Preincubation with staurosporine (1 mu M) blocke d the phorbol 12-myristate 13-acetate-induced decrease in secretion. N either forskolin (10 mu M) nor W-7 (20 mu M) had any effect on net tra nsport. Elevation of intracellular calcium activity with either A-2318 7 or thapsigargin produced a slight, transient decrease in transport. Addition of dopamine (1 mu M) to the peritubular side, but not the lum inal side, caused a significant (P < 0.01) decrease in net secretion. Both the alpha-adrenergic agonist oxymetazoline (10 mu M) and depletio n of intracellular Na+ transiently, but significantly (P < 0.05), incr eased net transport. The data indicate that renal organic anion excret ion may be regulated through dopaminergic inhibition and a-adrenergic stimulation of net transepithelial secretion.