Premium
Dopamine stimulates 45 Ca 2+ uptake through cAMP, PLC/PKC, and MAPKs in renal proximal tubule cells
Author(s) -
Han Ji Yeon,
Heo Jung Sun,
Lee Yun Jung,
Lee Jang Hern,
Taub Mary,
Han Ho Jae
Publication year - 2007
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.20956
Subject(s) - dopamine , staurosporine , endocrinology , protein kinase c , medicine , channel blocker , chemistry , agonist , protein kinase a , pharmacology , biology , kinase , calcium , receptor , biochemistry
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‐κB inhibitors SN50, TLCK, and Bay 11‐7082. In addition, dopamine significantly increased the level of NF‐κB 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‐κB activation. J. Cell. Physiol. 211: 486–494, 2007. © 2006 Wiley‐Liss, Inc.