Group VIA phospholipase A2 is a target for vasopressin signaling in the thick ascending limb.

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, iPLA2β, in the outer medulla of rats. In the present study, we therefore examined the contribution of iPLA2β to NKCC2 regulation. Immunoreactive iPLA2β 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 receptor-selective 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 iPLA2β abundance (−...