EVIDENCE FOR THE INVOLVEMENT OF AN ANION-EXCHANGER IN CORTISOL RELEASE FROM BOVINE ADRENOCORTICAL-CELLS

In this study the influence of probenecid as inhibitor of the renal ex cretory system for organic anions was tested on the release of cortiso l from primary cultures of bovine adrenocortical cells. ACTH-stimulate d cortisol release (30 min to 24 h) was inhibited by probenecid (K-i = 0.093 mM). Analysis of steroid synthesis with H-3-pregnenolone as pre cursor indicated that part of the inhibition resulted from an attenuat ion of steroid synthesis by probenecid. The increased intracellular co rtisol levels in the presence of probenecid however indicate an inhibi tory effect on an efflux mechanism. Cortisol efflux was trans-stimulat ed by p-aminohippurate (PAH) and tetrafluorosuccinate, substrates of t he renal PAH/anion exchanger; Further evidence for the PAH exchanger p rovided the expression of a probenecid-sensitive PAH transporter after injection of mRNA from adrenal cells into Xenopus laevis oocytes.