Regulatory mechanisms of Na/Pi cotransporter by glucocorticoid in renal proximal tubule cells: involvement of cAMP and PKC.
The signaling pathways involved in the regulation of glucocorticoid on Pi uptake were examined in primary cultured rabbit renal proximal tubule cells (PTCs). Dexamethasone (DEX, 10(-9) M) inhibited Pi uptake, although aldosterone, a mineralocorticoid, did not affect Pi uptake. Its effect was due to a 23% decrease in the V(max) value. DEX-induced inhibition of Pi uptake was prevented by actinomycin D, cycloheximide, and the glucocorticoid receptor antagonists, progesterone and cortexolone. SQ 22536 (adenylate cyclase inhibitor) and the myristoylated protein kinase A inhibitor amide 14-22 (PKI) did not block the DEX-induced inhibition of Pi uptake. Indeed, DEX did not affect cAMP production. However, neomycin and U 73122 (PLC inhibitors), staurosporine and bisindolylmaleimide I (PKC inhibitors) blocked the DEX-induced inhibition of Pi uptake. In addition, DEX increased the membrane-bound PKC activity from 2. 82+/-0.21 to 4.16+/-0.34 pmol/mg protein/min. These findings demonstrate that glucocorticoid inhibits Pi uptake and its effect is genomic and receptor-mediated and the activation of the PLC/PKC pathway is involved in its effect on the PTCs.
Xan
H J
HJ
Department of Veterinary Physiology, College of Veterinary Medicine, Hormone Research Center, Chonnam National University, Kwangju, Korea. hjhan@chonnam.chonnam.ac.kr
Kim
D H
DH
Park
S H
SH
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology / Q000502:physiology*; D066298:In Vitro Techniques; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000378:metabolism*; D008297:Male; D010710:Phosphates / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011817:Rabbits; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000502:physiology; D012964:Sodium / Q000378:metabolism; D050608:Sodium-Phosphate Cotransporter Proteins; D027981:Symporters
D002352:Carrier Proteins; D005938:Glucocorticoids; D010710:Phosphates; D011500:Protein Synthesis Inhibitors; D011965:Receptors, Glucocorticoid; D050608:Sodium-Phosphate Cotransporter Proteins; D027981:Symporters; D003609:Dactinomycin; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D003907:Dexamethasone; D003513:Cycloheximide; D012964:Sodium; D000242:Cyclic AMP; D011493:Protein Kinase C