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

被引:110
作者
Traebert, M
Völkl, H
Biber, J
Murer, H
Kaissling, B
机构
[1] Univ Zurich, Inst Anat, CH-8057 Zurich, Switzerland
[2] Univ Zurich, Inst Physiol, CH-8057 Zurich, Switzerland
[3] Univ Innsbruck, Inst Physiol, A-6020 Innsbruck, Austria
关键词
isolated proximal tubule; immunohistochemistry; parathyroid hormone receptor; type IIa sodium-phosphate transporter; protein kinase A; protein kinase C;
D O I
10.1152/ajprenal.2000.278.5.F792
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Parathyroid hormone (PTH) inhibits proximal tubular reabsorption of Pi by retrieval of type IIa Na-Pi cotransporters (NaPi-IIa) from the brush-border membrane (BBM). We analyzed by immunohistochemistry whether PTH analogs, signaling 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 proximal tubule in vitro a retrieval of NaPi-IIa and whether pharmacological agonists or inhibitors of these kinases are able to either mimic or interfere with these PTH effects. Treatment with either 1-34 or 3-34 PTH downregulated NaPi-IIa in rat kidney. In isolated murine proximal tubules 1-34 PTH was effective when added to either the apical or basolateral perfusate, whereas 3-34 PTH acted only via the luminal perfusate. These effects were mimicked by an activation of PKA with 8-bromoadenosine 3',5'-cyclic monophosphate or PKC with 1,2-dioctanoylglycerol. The luminal action of both PTH peptides 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 can be internalized by cAMP-dependent and -independent signaling mechanisms; 2) functional PTH receptors are located in both membrane domains; and 3) apical PTH receptors may preferentially initiate the effect through a PKC-dependent mechanism.
引用
收藏
页码:F792 / F798
页数:7
相关论文
共 41 条
[1]   MODE OF ACTION OF PARATHYROID HORMONE AND CYCLIC ADENOSINE 3',5'-MONOPHOSPHATE ON RENAL TUBULAR PHOSPHATE REABSORPTION IN DOG [J].
AGUS, ZS ;
PUSCHETT, JB ;
SENESKY, D ;
GOLDBERG, M .
JOURNAL OF CLINICAL INVESTIGATION, 1971, 50 (03) :617-&
[2]   EFFECT OF PARATHYROID-HORMONE AND CYCLIC ADENOSINE-3',5'-MONOPHOSPHATE ON ISOTONIC FLUID REABSORPTION - POLARITY OF PROXIMAL TUBULAR CELLS [J].
BAUMANN, K ;
CHAN, YL ;
BODE, F ;
PAPAVASSILIOU, F .
KIDNEY INTERNATIONAL, 1977, 11 (02) :77-85
[3]   Renal expression of Na+ phosphate cotransporter mRNA and protein: Effect of the Gy mutation and low phosphate diet [J].
Beck, L ;
Meyer, RA ;
Meyer, MH ;
Biber, J ;
Murer, H ;
Tenenhouse, HS .
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 1996, 431 (06) :936-941
[4]   Targeted inactivation of Npt2 in mice leads to severe renal phosphate wasting, hypercalciuria, and skeletal abnormalities [J].
Beck, L ;
Karaplis, AC ;
Amizuka, N ;
Hewson, AS ;
Ozawa, H ;
Tenenhouse, HS .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (09) :5372-5377
[5]   PREPARATION AND STUDY OF FRAGMENTS OF SINGLE RABBIT NEPHRONS [J].
BURG, M ;
GRANTHAM, J ;
ABRAMOW, M ;
ORLOFF, J .
AMERICAN JOURNAL OF PHYSIOLOGY, 1966, 210 (06) :1293-&
[6]   PTH SENSITIVE ADENYL-CYCLASE ACTIVITY IN DIFFERENT SEGMENTS OF RABBIT NEPHRON [J].
CHABARDES, D ;
IMBERT, M ;
CLIQUE, A ;
MONTEGUT, M ;
MOREL, F .
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 1975, 354 (03) :229-239
[7]   ADENYLATE-CYCLASE RESPONSIVENESS TO HORMONES IN VARIOUS PORTIONS OF THE HUMAN NEPHRON [J].
CHABARDES, D ;
GAGNANBRUNETTE, M ;
IMBERTTEBOUL, M ;
GONTCHAREVSKAIA, O ;
MONTEGUT, M ;
CLIQUE, A ;
MOREL, F .
JOURNAL OF CLINICAL INVESTIGATION, 1980, 65 (02) :439-448
[8]   PARATHYROID-HORMONE FRAGMENT [3-34] STIMULATES PROTEIN-KINASE-C (PKC) ACTIVITY IN RAT OSTEOSARCOMA AND MURINE T-LYMPHOMA CELLS [J].
CHAKRAVARTHY, BR ;
DURKIN, JP ;
RIXON, RH ;
WHITFIELD, JF .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1990, 171 (03) :1105-1110
[9]   PARATHYROID FUNCTION AND RENAL EXCRETION OF 3'5'-ADENYLIC ACID [J].
CHASE, LR ;
AURBACH, GD .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1967, 58 (02) :518-&
[10]   REGULATION OF SODIUM-DEPENDENT PHOSPHATE-TRANSPORT BY PARATHYROID-HORMONE IN OPOSSUM KIDNEY-CELLS - ADENOSINE 3',5'-MONOPHOSPHATE-DEPENDENT AND 3',5'-MONOPHOSPHATE-INDEPENDENT MECHANISMS [J].
COLE, JA ;
FORTE, LR ;
EBER, S ;
THORNE, PK ;
POELLING, RE .
ENDOCRINOLOGY, 1988, 122 (06) :2981-2989