title: Dopamine stimulates 45Ca2+ uptake through cAMP, PLC/PKC, and MAPKs in renal proximal tubule cells.
abstract: We have examined the effect of dopamine on Ca(2+) uptake and its related signaling pathways in primary renal proximal tubule cells (PTCs). Dopamine increased Ca(2+) uptake in a concentration (>10(-10) M) and time- (>8 h) dependent manner. Dopamine-induced increase in Ca(2+) uptake was prevented by SCH 23390 (a DA(1) antagonist) rather than spiperone (a DA(2) antagonist). SKF 38393 (a DA(1) agonist) increased Ca(2+) uptake unlike the case with quinpirole (a DA(2) agonist). Dopamine-induced increase in Ca(2+) uptake was blocked by nifedipine and methoxyverapamil (L-type Ca(2+) channel blockers). Moreover, dopamine-induced increase in Ca(2+) uptake was blocked by pertussis toxin (a G(i) protein inhibitor), protein kinase A (PKA) inhibitor amide 14/22 (a PKA inhibitor), and SQ 22536 (an adenylate cyclase inhibitor). Subsequently, dopamine increased cAMP level. The PLC inhibitors (U 73122 and neomycin), the PKC inhibitors (staurosporine and bisindolylmaleimide I) suppressed the dopamine-induced increase of Ca(2+) uptake. SB 203580 (a p38 MAPK inhibitor) and PD 98059 (a MAPKK inhibitor) also inhibited the dopamine-induced increase of Ca(2+) uptake. Dopamine-induced p38 and p42/44 MAPK phosphorylation was blocked by SQ 22536, neomycin, and staurosporine. The stimulatory effect of dopamine on Ca(2+) uptake was significantly inhibited by the NF-kappaB inhibitors SN50, TLCK, and Bay 11-7082. In addition, dopamine significantly increased the level of NF-kappaB p65, which was prevented by either SQ 22536, neomycin, staurosporine, PD 98059, or SB 203580. Thus, dopamine stimulates Ca(2+) uptake in PTCs, initially through by G(s) coupled dopamine receptors, PLC/PKC, followed by MAPK, and ultimately by NF-kappaB activation.
authors.affiliation: Department of Veterinary Physiology, Biotherapy Human Resources Center, College of Veterinary Medicine, Chonnam National University, Gwangju, Korea.
authors.forename: Ji Yeon
authors.initials: JY
authors.lastname: Han
authors.forename: Jung Sun
authors.initials: JS
authors.lastname: Heo
authors.forename: Yun Jung
authors.initials: YJ
authors.lastname: Lee
authors.forename: Jang Hern
authors.initials: JH
authors.lastname: Lee
authors.forename: Mary
authors.initials: M
authors.lastname: Taub
authors.forename: Ho Jae
authors.initials: HJ
authors.lastname: Han
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism; D002132:Calcium Radioisotopes / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D011817:Rabbits; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D013997:Time Factors; D010738:Type C Phospholipases / Q000378:metabolism*
chemical_list: D020746:Calcium Channels, L-Type; D002132:Calcium Radioisotopes; D016328:NF-kappa B; D017447:Receptors, Dopamine D1; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D010738:Type C Phospholipases; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D000262:Adenylyl Cyclases; D002118:Calcium; D004298:Dopamine