We examined the effect of glucocorticoids on brush border membrane transporters and, furthermore, the involvement of Ca
2+ in its action in the primary cultured rabbit renal proximal tubule cells (PTCs). Dexamethasone (DEX, 10
-9 M) decreased Pi uptake by 17%; whereas DEX affected neither α-methyl-glucopyranoside (α-MG) uptake nor Na
+ uptake. The DEX-induced inhibition of Pi uptake was due to a decrease of V
max. In contrast, other steroid hormones such as progesterone, testosterone, and 17β-estradiol (10
-9 M) did not induce inhibition of Pi uptake. In order to examine the involvement of Ca
2+ in DEX-induced inhibition of Pi uptake, PTCs were treated with A 23187 (10
-6 M, Ca
2+ ionophore). A 23187 also inhibited Pi uptake, mimicking DEX action in Pi uptake. Treatments with W-7 (10
-4 M, calmodulin dependent kinase inhibitor), KN-62 (10
-6 M, Ca
2+/calmodulin-dependent protein kinase II inhibitor), and BAPTA/AM (10
-6 M) or TMB-8 (10
-4 M) (intracellular Ca
2+ mobilization blockers) blocked the DEX-induced inhibition of Pi uptake. However, nifedifine, methoxyverapamil (10
-6 M, L-type Ca
2+ channel blockers), and EGTA (1 mM, extracellular Ca
2+ chelator) did not block it. In conclusion, DEX inhibited Pi uptake via, in part, Ca
2+/calmodulin pathway mediated by intracellular Ca
2+ mobilization in the PTCs.
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