title: Epidermal growth factor regulates Ca2+ uptake in primary cultured renal proximal tubule cells: involvement of cAMP, PKC and cPLA2.
abstract: Epidermal growth factor (EGF) is known to play an important role in modulating renal transport functions. Thus, we investigated the effect of EGF on Ca(2+) uptake and its related signals in the primary cultured rabbit renal proximal tubule cells. EGF (50 ng/ml, 1 h) stimulated Ca(2+) uptake. Its effect was blocked by AG 1478 (an EGF receptor antagonist), genistein or herbimycin A (tyrosine kinase inhibitors). EGF increased intracellular cAMP level and SQ 22536 (an adenylate cyclase inhibitor), Rp-cAMP (a cAMP analogue), or PKI (a protein kinase A inhibitor) blocked the EGF-induced stimulation of Ca(2+) uptake. EGF-induced stimulation of Ca(2+) uptake was also blocked by neomycin or U-73122 (phospholipase C inhibitors), staurosporine, H-7, or bisindolylmaleimide I (protein kinase C inhibitors), nifedipine or methoxyverapamil (L-type Ca(2+) channel blockers). It increased IPs formation by 167 +/- 5% compare to control within 90 s. On the other hand, EGF increased [(3)H]-arachidonic acid release, which was significantly blocked by PKC inhibitors. In addition, PGE(2), one of cyclooxygenase metabolites, and 5,6-EET, one of cytochrome P-450 metabolites, increased Ca(2+) uptake. These results suggest that cAMP, PLC/PKC, and PLA(2) are involved in EGF-induced stimulation of Ca(2+) uptake.
authors.affiliation: Department of Veterinary Physiology, College of Veterinary Medicine, Biotechnology Research Institute, Chonnam National University, Gwangju, Korea. hjhan@chonnam.ac.kr
authors.forename: Ho Jae
authors.initials: HJ
authors.lastname: Han
authors.forename: Soo Hyun
authors.initials: SH
authors.lastname: Park
authors.forename: Yun Jung
authors.initials: YJ
authors.lastname: Lee
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D016227:Benzoquinones; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D002132:Calcium Radioisotopes; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D047029:Lactams, Macrocyclic; D008297:Male; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011809:Quinones / Q000494:pharmacology; D011817:Rabbits; D017828:Rifabutin / Q000031:analogs & derivatives
chemical_list: D016227:Benzoquinones; D002132:Calcium Radioisotopes; D004791:Enzyme Inhibitors; D047029:Lactams, Macrocyclic; D011809:Quinones; D017828:Rifabutin; D016718:Arachidonic Acid; D004815:Epidermal Growth Factor; C020754:herbimycin; D000242:Cyclic AMP; D011493:Protein Kinase C; D010741:Phospholipases A; D002118:Calcium