Maturational changes in rabbit renal cortical phospholipase A2 activity

Ji Nan Sheu, Michel Baum, Elizabeth W. Harkins, Raymond Quigley

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Several studies have demonstrated that the neonatal kidney has a markedly attenuated response to parathyroid hormone (PTH); however, the cause for this blunted response is unknown. PTH stimulated cAMP production by 215 ± 18% in neonatal proximal tubule suspensions compared to a 35 ± 7% increase in adult proximal tubules. Thus, neonatal proximal tubules have functioning PTH receptors and a greater adenylate cyclase response than the adult segment. In adult proximal tubules, PTH stimulates phospholipase A2 (PLA2) activity and the inhibition of Na,K-ATPase activity by PTH is blocked by inhibitors of PLA2. We examined whether maturational changes in renal cortical activity could play a role in the attenuated response to PTH in the neonatal proximal tubule. Com pared to adults, neonates had a lower renal cortical cytosolic PLA2 (cPLA2) activity, assessed as the release of 14C- arachidonic acid (AA) from labeled phosphatidyl choline (0.44 ± 0.10 vs. 0.74 ± 0.06% 14C-AA released/min/mg protein, P < 0.05) and microsomal PLA2 activity (0.32 ± 0.03 vs. 1.20 ± 0.13% 14C-AA released/min/mg protein, P < 0.001). The protein abundance of cPLA2 was not different between the neonatal and adult renal cortex as assessed by immunoblot assay. Thus, the difference in activities must be due to a difference in regulation of cPLA2. Annexin 1 (lipocortin 1) has been shown to inhibit PLA2 activity by binding to phospholipid substrate. Annexin 1 protein abundance was higher in neonatal than in adult renal cortex (P < 0.001). Thus, the lower activity of PLA2 in the neonatal tubules may be due in part to higher expression of annexin 1. PLA2 activation by PTH, 8-bromo-cAMP and PMA was assessed as 3H- AA release from prelabeled suspensions of neonatal and adult proximal tubules. PTH (10-7 M), 8-bromo-cAMP (10-4 M) and PMA (5 x 10-8 M) significantly increased 3H-AA release from adult tubules (P < 0.05) but had no effect on neonatal tubules (P = NS). Thus, PTH, 8-bromo-cAMP and PMA stimulated PLA2 in adult but not neonatal proximal tubules. In conclusion, the maturational changes in renal cortical PLA2 activity may be a factor in the blunted response of neonatal proximal tubules to PTH.

Original languageEnglish (US)
Pages (from-to)71-78
Number of pages8
JournalKidney International
Volume52
Issue number1
StatePublished - 1997

Fingerprint

Phospholipases A2
Parathyroid Hormone
Rabbits
Kidney
Arachidonic Acid
8-Bromo Cyclic Adenosine Monophosphate
Annexins
Parathyroid Hormone Receptors
Suspensions
Proteins
Phospholipase A2 Inhibitors
Annexin A1
Cytosolic Phospholipases A2
Phosphatidylcholines
Adenylyl Cyclases
Phospholipids

Keywords

  • Phospholipase A
  • Proximal tubule
  • PTH
  • Renal cortex

ASJC Scopus subject areas

  • Nephrology

Cite this

Maturational changes in rabbit renal cortical phospholipase A2 activity. / Sheu, Ji Nan; Baum, Michel; Harkins, Elizabeth W.; Quigley, Raymond.

In: Kidney International, Vol. 52, No. 1, 1997, p. 71-78.

Research output: Contribution to journalArticle

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abstract = "Several studies have demonstrated that the neonatal kidney has a markedly attenuated response to parathyroid hormone (PTH); however, the cause for this blunted response is unknown. PTH stimulated cAMP production by 215 ± 18{\%} in neonatal proximal tubule suspensions compared to a 35 ± 7{\%} increase in adult proximal tubules. Thus, neonatal proximal tubules have functioning PTH receptors and a greater adenylate cyclase response than the adult segment. In adult proximal tubules, PTH stimulates phospholipase A2 (PLA2) activity and the inhibition of Na,K-ATPase activity by PTH is blocked by inhibitors of PLA2. We examined whether maturational changes in renal cortical activity could play a role in the attenuated response to PTH in the neonatal proximal tubule. Com pared to adults, neonates had a lower renal cortical cytosolic PLA2 (cPLA2) activity, assessed as the release of 14C- arachidonic acid (AA) from labeled phosphatidyl choline (0.44 ± 0.10 vs. 0.74 ± 0.06{\%} 14C-AA released/min/mg protein, P < 0.05) and microsomal PLA2 activity (0.32 ± 0.03 vs. 1.20 ± 0.13{\%} 14C-AA released/min/mg protein, P < 0.001). The protein abundance of cPLA2 was not different between the neonatal and adult renal cortex as assessed by immunoblot assay. Thus, the difference in activities must be due to a difference in regulation of cPLA2. Annexin 1 (lipocortin 1) has been shown to inhibit PLA2 activity by binding to phospholipid substrate. Annexin 1 protein abundance was higher in neonatal than in adult renal cortex (P < 0.001). Thus, the lower activity of PLA2 in the neonatal tubules may be due in part to higher expression of annexin 1. PLA2 activation by PTH, 8-bromo-cAMP and PMA was assessed as 3H- AA release from prelabeled suspensions of neonatal and adult proximal tubules. PTH (10-7 M), 8-bromo-cAMP (10-4 M) and PMA (5 x 10-8 M) significantly increased 3H-AA release from adult tubules (P < 0.05) but had no effect on neonatal tubules (P = NS). Thus, PTH, 8-bromo-cAMP and PMA stimulated PLA2 in adult but not neonatal proximal tubules. In conclusion, the maturational changes in renal cortical PLA2 activity may be a factor in the blunted response of neonatal proximal tubules to PTH.",
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AB - Several studies have demonstrated that the neonatal kidney has a markedly attenuated response to parathyroid hormone (PTH); however, the cause for this blunted response is unknown. PTH stimulated cAMP production by 215 ± 18% in neonatal proximal tubule suspensions compared to a 35 ± 7% increase in adult proximal tubules. Thus, neonatal proximal tubules have functioning PTH receptors and a greater adenylate cyclase response than the adult segment. In adult proximal tubules, PTH stimulates phospholipase A2 (PLA2) activity and the inhibition of Na,K-ATPase activity by PTH is blocked by inhibitors of PLA2. We examined whether maturational changes in renal cortical activity could play a role in the attenuated response to PTH in the neonatal proximal tubule. Com pared to adults, neonates had a lower renal cortical cytosolic PLA2 (cPLA2) activity, assessed as the release of 14C- arachidonic acid (AA) from labeled phosphatidyl choline (0.44 ± 0.10 vs. 0.74 ± 0.06% 14C-AA released/min/mg protein, P < 0.05) and microsomal PLA2 activity (0.32 ± 0.03 vs. 1.20 ± 0.13% 14C-AA released/min/mg protein, P < 0.001). The protein abundance of cPLA2 was not different between the neonatal and adult renal cortex as assessed by immunoblot assay. Thus, the difference in activities must be due to a difference in regulation of cPLA2. Annexin 1 (lipocortin 1) has been shown to inhibit PLA2 activity by binding to phospholipid substrate. Annexin 1 protein abundance was higher in neonatal than in adult renal cortex (P < 0.001). Thus, the lower activity of PLA2 in the neonatal tubules may be due in part to higher expression of annexin 1. PLA2 activation by PTH, 8-bromo-cAMP and PMA was assessed as 3H- AA release from prelabeled suspensions of neonatal and adult proximal tubules. PTH (10-7 M), 8-bromo-cAMP (10-4 M) and PMA (5 x 10-8 M) significantly increased 3H-AA release from adult tubules (P < 0.05) but had no effect on neonatal tubules (P = NS). Thus, PTH, 8-bromo-cAMP and PMA stimulated PLA2 in adult but not neonatal proximal tubules. In conclusion, the maturational changes in renal cortical PLA2 activity may be a factor in the blunted response of neonatal proximal tubules to PTH.

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