Regulatory mechanism of polarized membrane transport by glucocorticoid in renal proximal tubule cells: involvement of [Ca2+]i.
We examined the effect of glucocorticoids on brush border membrane transporters and, furthermore, the involvement of Ca2+ 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 alpha-methyl-glucopyranoside (alpha-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 17beta-estradiol (10(-9) M) did not induce inhibition of Pi uptake. In order to examine the involvement of Ca2+ in DEX-induced inhibition of Pi uptake, PTCs were treated with A 23187 (10(-6) M, Ca2+ 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, Ca2+/calmodulin-dependent protein kinase II inhibitor), and BAPTA/AM (10(-6) M) or TMB-8 (10(-4) M) (intracellular Ca2+ mobilization blockers) blocked the DEX-induced inhibition of Pi uptake. However, nifedifine, methoxyverapamil (10(-6) M, L-type Ca2+ channel blockers), and EGTA (1 mM, extracellular Ca2+ chelator) did not block it. In conclusion, DEX inhibited Pi uptake via, in part, Ca2+/calmodulin pathway mediated by intracellular Ca2+ mobilization in the PTCs.
Han
H J
HJ
Department of Veterinary Physiology, College of Veterinary Medicine, Hormone Research Center, Chonnam National University, Kwangju, Korea.
Kim
D H
DH
Park
S H
SH
Lee
Y S
YS
Lee
J H
JH
Yang
S I
SI
D000469:Alkaline Phosphatase / Q000032:analysis; D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000502:physiology*; D002455:Cell Division; D002478:Cells, Cultured; D003907:Dexamethasone / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology; D005938:Glucocorticoids / Q000493:pharmacokinetics / Q000502:physiology*; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000502:physiology*; D007931:Leucyl Aminopeptidase / Q000032:analysis; D008297:Male; D008871:Microvilli / Q000502:physiology; D010710:Phosphates / Q000502:physiology; D011374:Progesterone / Q000494:pharmacology; D011817:Rabbits / Q000502:physiology*; D012588:Scintillation Counting / Q000662:veterinary; D013739:Testosterone / Q000494:pharmacology; D005723:gamma-Glutamyltransferase / Q000032:analysis
D005938:Glucocorticoids; D010710:Phosphates; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol; D003907:Dexamethasone; D005723:gamma-Glutamyltransferase; D000469:Alkaline Phosphatase; D007931:Leucyl Aminopeptidase; D002118:Calcium