Dopamine stimulates 45Ca2+ uptake through cAMP, PLC/PKC, and MAPKs in renal proximal tubule cells

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Han, Ji Yeon; Heo, Jung Sun; Lee, Yun Jung; Lee, Jang-Hern; Taub, Mary; Han, Ho Jae

Issue Date
John Wiley & Sons
J Cell Physiol 211:486-494
We have examined the effect of dopamine on Ca2+ uptake and its related signaling pathways in primary renal proximal tubule cells (PTCs). Dopamine increased Ca2+ uptake in a concentration (>10-10 M) and time- (>8 h) dependent manner. Dopamine-induced increase in Ca2+ uptake was prevented by SCH 23390 (a DA1 antagonist) rather than spiperone (a DA2 antagonist). SKF 38393 (a DA1 agonist) increased Ca2+ uptake unlike the case with quinpirole (a DA2 agonist). Dopamine-induced increase in Ca2+ uptake was blocked by nifedipine and methoxyverapamil (L-type Ca2+ channel blockers). Moreover, dopamine-induced increase in Ca2+ uptake was blocked by pertussis toxin (a Gi 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 Ca2+ uptake. SB 203580 (a p38 MAPK inhibitor) and PD 98059 (a MAPKK inhibitor) also inhibited the dopamine-induced increase of Ca2+ uptake. Dopamine-induced p38 and p42/44 MAPK phosphorylation was blocked by SQ 22536, neomycin, and staurosporine. The stimulatory effect of dopamine on Ca2+ uptake was significantly inhibited by the NF-B inhibitors SN50, TLCK, and Bay 11-7082. In addition, dopamine significantly increased the level of NF-B p65, which was prevented by either SQ 22536, neomycin, staurosporine, PD 98059, or SB 203580. Thus, dopamine stimulates Ca2+ uptake in PTCs, initially through by Gs coupled dopamine receptors, PLC/PKC, followed by MAPK, and ultimately by NF-B activation.
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College of Veterinary Medicine (수의과대학)Dept. of Veterinary Medicine (수의학과)Journal Papers (저널논문_수의학과)
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