Maturational changes in rabbit renal cortical phospholipase A2 activity.
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. Compared 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.
Sheu
J N
JN
Department of Pediatrics, University of Texas Southwestern Medical Center at Dallas, USA.
Baum
M
M
Harkins
E W
EW
Quigley
R
R
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D017305:Annexin A1 / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D003907:Dexamethasone / Q000494:pharmacology; D066298:In Vitro Techniques; D007672:Kidney Cortex / Q000201:enzymology*; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology; D010281:Parathyroid Hormone / Q000494:pharmacology; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D011817:Rabbits; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D017305:Annexin A1; D010281:Parathyroid Hormone; D015124:8-Bromo Cyclic Adenosine Monophosphate; D003907:Dexamethasone; D000242:Cyclic AMP; D010741:Phospholipases A; D054467:Phospholipases A2; D013755:Tetradecanoylphorbol Acetate