Calcitriol upregulates expression and activity of the 1b isoform of the plasma membrane calcium pump in immortalized distal kidney tubular cells

The plasma membrane calcium pump (PMCA) is ubiquitously expressed in calciu m transporting epithelia. PMCA is encoded by four distinct genes (PMCA1-4) which can be further posttranscriptionally modified, PMCA1b is the only iso form of PMCA1 expressed in kidney and intestine. Calcitriol upregulates PMC A protein expression and activity and PMCA1 mRNA expression in the intestin e. Calcitriol has a similar effect on kidney distal tubule PMCA activity in vivo but the cellular basis for this effect has not been studied. PMCA exp ression in Madin-Darby bovine kidney (MDBK) cells, a distal kidney tubule c ell line, was compared with a proximal tubule (LLC-PK1) and embryonic (HEK 293) kidney cell line. Only MDBK cells express PMCA1b mRNA and PMCA protein . In MDBK cells, calcitriol increased steady state expression of PMCA1b mRN A and protein and upregulated the functional activity of PMCA on calcium tr ansport to a similar degree. Furthermore, calcitriol enhanced PMCA1b mRNA s tability. These data are consistent with in vivo localization studies demon strating the distal kidney tubule localization of PMCA protein, Furthermore , they indicate that calcitriol is an important regulator of PMCA activity in the kidney distal tubule by a pathway that includes translation and post transcriptional modification of PMCA1b. (C) 2000 Academic Press.