M. Traebert et al., Luminal and contraluminal action of 1-34 and 3-34 PTH peptides on renal type IIa Na-P-i cotransporter, AM J P-REN, 278(5), 2000, pp. F792-F798
Parathyroid hormone (PTH) inhibits proximal tubular reabsorption of Pi by r
etrieval of type IIa Na-Pi cotransporters (NaPi-IIa) from the brush-border
membrane (BBM). We analyzed by immunohistochemistry whether PTH analogs, si
gnaling through either protein kinase A (PKA) and C (PKC; 1-34 PTH) or only
PKC (3-34 PTH), elicit in rat kidney in vivo or in the perfused murine pro
ximal tubule in vitro a retrieval of NaPi-IIa and whether pharmacological a
gonists or inhibitors of these kinases are able to either mimic or interfer
e with these PTH effects. Treatment with either 1-34 or 3-34 PTH downregula
ted NaPi-IIa in rat kidney. In isolated murine proximal tubules 1-34 PTH wa
s effective when added to either the apical or basolateral perfusate, where
as 3-34 PTH acted only via the luminal perfusate. These effects were mimick
ed by an activation of PKA with 8-bromoadenosine 3',5'-cyclic monophosphate
or PKC with 1,2-dioctanoylglycerol. The luminal action of both PTH peptide
s was blocked by inhibition of the PKC pathway (calphostin C), whereas the
basolateral effect of 1-34 PTH was completely abolished by inhibiting both
pathways (H-89 and calphostin C). These results suggest that I) NaPi-IIa ca
n be internalized by cAMP-dependent and -independent signaling mechanisms;
2) functional PTH receptors are located in both membrane domains; and 3) ap
ical PTH receptors may preferentially initiate the effect through a PKC-dep
endent mechanism.