Maturational changes in rabbit renal cortical phospholipase A2 activity

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. 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.

Parathyroid hormone increases cytosolic calcium in neonatal nephron through protein kinase C pathway

“…It is noteworthy that parathyroid hormone (PTH), which plays a central role in the positive balance of calcium, is less efficient in inducing phosphaturia in human and rat neonates than in adults of the same species. This is probably due to a lower number of receptors, which increase with age [1] or to a lower cytosolic phospholipase A 2 activity [2], and minimizes urinary phosphate losses. Phosphate and calcium are important minerals for augmenting body mass.…”

Protein Kinase A Inhibits Leukotriene Synthesis by Phosphorylation of 5-Lipoxygenase on Serine 523

“…Activation of PKA can lead to phosphorylation of cPLA 2 (19,21) and can decrease the release of AA (22,23). Alternatively, activation of PKA can be without effect (24) or can increase (25) the release of AA in other circumstances, perhaps because AA may be released by PLA 2 s other than cPLA 2 . There are, to our knowledge, no reports of PKA inhibition of either the 12-LO or the 15-LO pathways, suggesting that these pathways are able to obtain AA during PKA activation and that these LOs are not inhibited by PKA.…”

1α,25(OH)2D3 and parathyroid hormone (PTH) signaling in rat intestinal cells: activation of cytosolic PLA2

“…Activation of PLA2 by 1␣,25(OH) 2 D 3 was demostrated in other cell types, such as skeletal muscle cells [10], chondrocytes [11] and hepatocytes [12]. Furthermore, stimulation of cPLA2 by PTH has been reported in renal cells [13].…”