Luminal and contraluminal action of 1-34 and 3-34 PTH peptides on renal type IIa Na-P-i cotransporter

Citation
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
Citations number
41
Categorie Soggetti
da verificare
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
ISSN journal
03636127 → ACNP
Volume
278
Issue
5
Year of publication
2000
Pages
F792 - F798
Database
ISI
SICI code
0363-6127(200005)278:5<F792:LACAO1>2.0.ZU;2-V
Abstract
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.