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.
Steffgen
J
J
Abteilung für Nephrologie und Rheumatologie, Universität Göttingen, Deutschland. jsteffgen@veg-physiol.med.uni-goettingen.de
Rohrbach
S
S
Beery
E
E
Ersoy
D
D
Jarry
H
H
Metten
M
M
Bornstein
S R
SR
Müller
G A
GA
Burckhardt
G
G
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