Paliege, A., Roeschel, T., Neymeyer, H., Seidel, S., Kahl, T., Daigeler, A. L., Mutig, K., Mrowka, R., Ferreri, N. R., Wilson, B. S., Himmerkus, N., Bleich, Markus and Bachmann, S. (2012) Group VIA phospholipase A2 is a target for vasopressin signaling in the thick ascending limb. American Journal of Physiology-Renal Physiology, 302 (7). F865-F874. DOI 10.1152/ajprenal.00222.2011.

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Abstract

Group VIA phospholipase A2 is a target for vasopressin signaling in the thick ascending limb. Am J Physiol Renal Physiol 302: F865–F874, 2012. First published January 4, 2012; doi:10.1152/ajprenal.00222.2011.— Na�-K�-2Cl� cotransporter (NKCC2)-mediated NaCl reabsorption in the thick ascending limb (TAL) is stimulated by AVP via V2 receptor/PKA/cAMP signaling. This process is antagonized by locally produced eicosanoids such as 20-HETE or prostaglandin E2, which are synthesized in a phospholipase A2-dependent reaction cascade. Using microarray-based gene expression analysis, we found evidence for an AVP-dependent downregulation of the calcium-independent isoform of PLA2, iPLA2�, in the outer medulla of rats. In the present study, we therefore examined the contribution of iPLA2� to NKCC2 regulation. Immunoreactive iPLA2� protein was detected in cultured mTAL cells as well as in the entire TAL of rodents and humans with the exception of the macula densa. Administration of the V2 receptorselective agonist desmopressin (5 ng/h; 3 days) to AVP-deficient diabetes insipidus rats increased outer medullary phosphorylated NKCC2 (pNKCC2) levels more than twofold in association with a marked reduction in iPLA2� abundance (�65%; P � 0.05), thus confirming microarray results. Inhibition of iPLA2� in SpragueDawley rats with FKGK 11 (0.5 �M) or in mTAL cells with FKGK 11 (10 �M) or (S)-bromoenol lactone (5 �M) for 1 h markedly increased pNKCC2 levels without affecting total NKCC2 expression. Collectively, these data indicate that iPLA2� acts as an inhibitory modulator of NKCC2 activity and suggest that downregulation of iPLA2� may be a relevant step in AVP-mediated urine concentration.

Document Type:	Article
Research affiliation:	Kiel University Kiel University > Kiel Marine Science OceanRep > The Future Ocean - Cluster of Excellence
Refereed:	Yes
Open Access Journal?:	Yes
Publisher:	American Physiological Society
Projects:	Future Ocean
Date Deposited:	02 Feb 2018 11:30
Last Modified:	23 Sep 2019 20:19
URI:	https://oceanrep.geomar.de/id/eprint/41804

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