Parathyroid hormone stimulation of renal phosphoinositide metabolism is a cyclic nucleotide-independent effect

Meltzer, Victor N.; Weinreb, Steven L.; Bellorín-Font, Ezequiel; Hruska, Keith A.

doi:10.1016/0005-2760(82)90342-3

“…As reported previously (18,30), the phospholipids labeled in these experiments were PA, PtdIns 4-P, and Ptdlns(4,5)-P2. PtdIns(4,5)-P2 turnover stimulates 32Pi incorporation from ATP as a result of phosphorylation of PtdIns and PtdIns 4-P (1,2,20,39). Also, the product of Ptdlns(4,5)-P2 turnover, DAG, is phosphorylated to PA.…”

Section: Resultsmentioning

confidence: 99%

“…This would remove it from a mechanism of cell activation, and place it in the realm of a biologic response. However, other investigators (20,21) have not found a stimulation of phosphoinositide metabolism by cyclic AMP in the renal cortex. To date, no report has demonstrated production ofthe messages of Ptdlns(4,5)-P2 hydrolysis (1P3 and DAG) by PTH.…”

Section: Introductionmentioning

confidence: 88%

“…One such mechanism would be receptor-mediated Ptdlns(4,5)-P2 hydrolysis and Ins(1,4,5)-P3 production. Several investigators (18)(19)(20)(21) have shown an effect of PTH on renal tubular phosphoinositide metabolism, and one report shows the effect was present in the apical membrane of the proximal renal tubule (18). Some have reported that the stimulation of phosphoinositide metabolism by PTH was cyclic AMP dependent (19).…”

Section: Introductionmentioning

confidence: 99%

“…Plates were then washed with a cytoplasm-like buffer containing 100 mM KCI, 20 mM NaCI, 5 mM MgSO4, 0.96 mM NaH2PO4, 25 mM NaHCO3, and I mM EGTA. The calcium concentration was adjusted to either 20 nM or 3.3 uM.…”

Section: Introductionmentioning

confidence: 99%

“…Proximal tubular segments were isolated from the cortex of mongrel dog kidneys as previously described (20). The isolated proximal tubular segments were suspended in a modified Krebs-Hensleit bicarbonate buffer containing 5 mM glucose, 5 mM alanine, and 5 mM sodium lactate.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Stimulation of inositol trisphosphate and diacylglycerol production in renal tubular cells by parathyroid hormone.

Hruska¹,

Moskowitz²,

Esbrit³

et al. 1987

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ATP directly enhances calcium channels in the luminal membrane of the distal nephron

Brunette

¹

,

Mailloux

²

,

Hilal

³

1999

J. Cell. Phys.

1

0

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Calcium (Ca(2+)) transport by the distal tubule (DT) luminal membrane is regulated by the parathyroid hormone (PTH) and calcitonin (CT) through the action of messengers, protein kinases, and ATP as the phosphate donor. In this study, we questioned whether ATP itself, when directly applied to the cytosolic surface of the membrane could influence the Ca(2+) channels previously detected in this membrane. We purified the luminal membranes of rabbit proximal (PT) and DT separately and measured Ca(2+) uptake by these vesicles loaded with ATP or the carrier. The presence of 100 microM ATP in the DT membrane vesicles significantly enhanced 0.5 mM Ca(2+) uptake from 0.57 +/- 0.02 to 0.71 +/- 0.02 pmol/microg per 10 sec (P < 0. 01) in the absence of Na(+) and from 0.36 +/- 0.03 to 0.59 +/- 0.01 pmol/microg per 10 sec (P < 0.01) in the presence of 100 mM Na(+). This effect was dose dependent with an EC(50) value of approximately 40 microM. ATP action involved the high-affinity component of Ca(2+) transport, decreasing the Km from 0.08 +/- 0.01 to 0.04 +/- 0.01 mM (P< 0.02). Replacement of the nucleotide by the nonhydrolyzable ATPgammas abolished this action. Because ATP has been reported to be necessary for cytoskeleton integrity, we also investigated the effect of intravesicular cytochalasin on Ca(2+) transport. Inclusion of 20 microM cytochalasin B decreased 0.5 mM Ca(2+) uptake from 0.33 +/- 0.01 to 0.15 +/- 0.01 pmol/microg per 10 sec (P< 0.01). However, when both 100 microM ATP and 20 microM cytochalasin were present in the vesicles, the uptake was not different from that observed with ATP alone. Neither ATP nor cytochalasin had any influence on Ca(2+) uptake by the PT luminal membrane. We conclude that the high-affinity Ca(2+) channel of the DT luminal membrane is regulated by ATP and that ATP plays a crucial role in the integrity of the cytoskeleton which is also involved in the control of Ca(2+) channels within this membrane.

show abstract

ATP directly enhances calcium channels in the luminal membrane of the distal nephron

Brunette¹,

Mailloux²,

Hilal³

1999

J. Cell. Phys.

0

View full text Add to dashboard Cite

Calcium (Ca(2+)) transport by the distal tubule (DT) luminal membrane is regulated by the parathyroid hormone (PTH) and calcitonin (CT) through the action of messengers, protein kinases, and ATP as the phosphate donor. In this study, we questioned whether ATP itself, when directly applied to the cytosolic surface of the membrane could influence the Ca(2+) channels previously detected in this membrane. We purified the luminal membranes of rabbit proximal (PT) and DT separately and measured Ca(2+) uptake by these vesicles loaded with ATP or the carrier. The presence of 100 microM ATP in the DT membrane vesicles significantly enhanced 0.5 mM Ca(2+) uptake from 0.57 +/- 0.02 to 0.71 +/- 0.02 pmol/microg per 10 sec (P < 0. 01) in the absence of Na(+) and from 0.36 +/- 0.03 to 0.59 +/- 0.01 pmol/microg per 10 sec (P < 0.01) in the presence of 100 mM Na(+). This effect was dose dependent with an EC(50) value of approximately 40 microM. ATP action involved the high-affinity component of Ca(2+) transport, decreasing the Km from 0.08 +/- 0.01 to 0.04 +/- 0.01 mM (P< 0.02). Replacement of the nucleotide by the nonhydrolyzable ATPgammas abolished this action. Because ATP has been reported to be necessary for cytoskeleton integrity, we also investigated the effect of intravesicular cytochalasin on Ca(2+) transport. Inclusion of 20 microM cytochalasin B decreased 0.5 mM Ca(2+) uptake from 0.33 +/- 0.01 to 0.15 +/- 0.01 pmol/microg per 10 sec (P< 0.01). However, when both 100 microM ATP and 20 microM cytochalasin were present in the vesicles, the uptake was not different from that observed with ATP alone. Neither ATP nor cytochalasin had any influence on Ca(2+) uptake by the PT luminal membrane. We conclude that the high-affinity Ca(2+) channel of the DT luminal membrane is regulated by ATP and that ATP plays a crucial role in the integrity of the cytoskeleton which is also involved in the control of Ca(2+) channels within this membrane.

show abstract

Parathyroid hormone stimulation of renal phosphoinositide metabolism is a cyclic nucleotide-independent effect

Cited by 66 publications

References 24 publications

Stimulation of inositol trisphosphate and diacylglycerol production in renal tubular cells by parathyroid hormone.

Stimulation of inositol trisphosphate and diacylglycerol production in renal tubular cells by parathyroid hormone.

ATP directly enhances calcium channels in the luminal membrane of the distal nephron

ATP directly enhances calcium channels in the luminal membrane of the distal nephron

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