Demonstration of a probenecid-inhibitable anion exchanger involved in the release of cortisol and cAMP and in the uptake of p-aminohippurate in bovine adrenocortical cells.
Recently we provided evidence for the involvement of a probenecid-inhibitable anion exchanger in cortisol release from primary cultures of bovine adrenocortical cells. In the present study, we further characterized this exchange transporter. Adrenocorticotropic hormone stimulated 3H-p-aminohippurate (3H-PAH) uptake into as well as cortisol release from the cells about two- and tenfold, respectively. Probenecid inhibited both 3H-PAH uptake and cortisol release by about 55 and 63%. Preincubation of the cells with 1 mM PAH trans-stimulated 3H-PAH uptake by 30%, whereas cortisol release was inhibited by 30%. 3H-PAH uptake was cis-inhibited by 1 mM glutarate or by 1 mM cortisol in the medium, while cortisol release was trans-stimulated by glutarate. PAH in the incubation medium showed saturable cis-inhibition of 3H-PAH uptake. The release of cyclic adenosine monophosphate, a substrate of the renal PAH exchanger, was also inhibited by probenecid and trans-stimulated by glutarate. In summary, the trans-stimulation and cis-inhibition experiments support the concept of an anion exchanger involved in cortisol and cyclic adenosine monophosphate release from and PAH uptake into adrenocortical cells.
Abteilung für Nephrologie und Rheumatologie, Universität Göttingen, Deutschland. jsteffgen@veg-physiol.med.uni-goettingen.de
J
J
Steffgen
S
S
Rohrbach
E
E
Beery
D
D
Ersoy
H
H
Jarry
M
M
Metten
S R
SR
Bornstein
G A
GA
Müller
G
G
Burckhardt
D000302:Adrenal Cortex / Q000187:drug effects / Q000502:physiology*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D017920:Antiporters / Q000037:antagonists & inhibitors / Q000502:physiology*; D001692:Biological Transport / Q000187:drug effects; D002417:Cattle; D002478:Cells, Cultured; D003470:Culture Media; D000242:Cyclic AMP / Q000378:metabolism*; D005977:Glutarates / Q000494:pharmacology; D006854:Hydrocortisone / Q000378:metabolism* / Q000494:pharmacology; D007700:Kinetics; D011339:Probenecid / Q000494:pharmacology*; D014316:Tritium; D010130:p-Aminohippuric Acid / Q000493:pharmacokinetics*
D017920:Antiporters; D003470:Culture Media; D005977:Glutarates; D014316:Tritium; D000324:Adrenocorticotropic Hormone; D000242:Cyclic AMP; D011339:Probenecid; D006854:Hydrocortisone; D010130:p-Aminohippuric Acid