title: Regulatory mechanisms of Na/Pi cotransporter by glucocorticoid in renal proximal tubule cells: involvement of cAMP and PKC.
abstract: 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.
authors.affiliation: Department of Veterinary Physiology, College of Veterinary Medicine, Hormone Research Center, Chonnam National University, Kwangju, Korea. hjhan@chonnam.chonnam.ac.kr
authors.forename: H J
authors.initials: HJ
authors.lastname: Xan
authors.forename: D H
authors.initials: DH
authors.lastname: Kim
authors.forename: S H
authors.initials: SH
authors.lastname: Park
mesh_terms: 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
chemical_list: 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