2006 Fiscal Year Final Research Report Summary
The physiological role and localization of COX2, prostaglandin E2 and prostaglandin F2a in kidney
| Project/Area Number |
16590798
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | Jichi Medical University |
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Principal Investigator |
SAITO Osamu Jichi Medical University, School of Medicine, Assistant Professor, 医学部, 講師 (10285778)
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| Co-Investigator(Kenkyū-buntansha) |
KUSANO Eiji Jichi Medical University, Nephrology, Professor (50102249)
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| Project Period (FY) |
2004 – 2006
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| Keywords | Prostaglandin F2α / Prostaglandin E2 / Kidney / Fp receptor / signal transduction / rabbit / cloning |
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| Research Abstract |
PGF2α is one of the major prostanoids produced by the kidney and the most abndant prostaglandin detected in urine ; however, its renal effects are poorly characterized. The cellular effects of PGF2α are mediated by a G protein-coupled transmembrane receptor designated the FP receptor. The present study was performed to determine the cellular distribution of the mouse FP receptor and clone a PGF-prostanoid receptor (FP) from the rabbit kidney and determine the functional consequences of its activation.
At first, both in situ hybridization and β-galactosidase knocked into the endogenous FP locus were used to determine the cellular distribution of the mouse FP receptor. Specific labeling was detected in the kidney, ovary, and uterus. Abundant FP expression in ovarian follicles and uterus is consistent with previous reports of failed parturition in FP+/- mice. In the kidney, coexpression of the mFP mRNA with the thiazide-sensitive cotransporter defined its expression in the distal convolute
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d tubule (DCT). FP receptor was also present in aquaporin-2-positive cortical collecting ducts (CCD). No FP mRNA was detected in glomeruli, proximal tubules, or thick ascending limbs. Intrarenal expression of the FP receptor in the DCT and CCD suggests an important role for the FP receptor regulating water and solute transport in these segments of the nephron.
Next, nuclease protection assay showed that FP mRNA expression predominates in rabbit ovary and kidney. In situ hybridization revealed that renal FP expression predominates in the cortical collecting duct (CCD). Although FP receptor activation failed to increase intracellular Ca2+, it potently inhibited vasopressin-stimulated osmotic water permeability (Lp,10^<-7> cm/(atm-s)) in in vitro microperfused rabbit CCDs. Inhibition of Lp by the FP selective agonist latanoprost was additive to inhibition of vasopressin action by the EP selective agonist sulprostone. Inhibition of Lp by latanoprost was completely blocked by pertussis toxin, consistent with a Gi-coupled mechanism. Heterologous transfection of the rabbit FP cDNA into HEK293 cells also showed that latanoprost inhibited cAMP generation via a pertussis toxin-sensitive mechanism but did not increase cell Ca2+. These studies demonstrate a functional FP receptor on the basolateral membrane of rabbit CCDs. In contrast to the Ca2+ signal transduced by other FP receptors, this renal FP receptor signals via a pertussis toxin-sensitive mechanism that is not coupled to cell Ca2+. Less
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Research Products
(12 results)
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[Journal Article] A case of thoracic hemorrhage due to ectopic parathyroid hyperplasia with renal failure.2005
Author(s)
Akimoto, T., Saito, O., Muto, S., Hasegawa, T., Nokubi, M., Numata, A., Ando, Y, Sohara, Y, Saito, K, Kusano E.
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Journal Title
Am J Kidney Dis 45(6)
Pages: e109-e114
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Characterization of a rabbit kidney prostaglandin F2_receptor exhibiting Gi-restricted signaling that inhibits water absorption in the collecting duct.2005
Author(s)
Hebert, R.L., Carmosino, M., Saito, O., Yang, G., Jackson, C.A., Qi, Z., Breyer, R.M., Natarajan, C., Hata, A.N., Zhang, Y, Guan, Y., Breyer, M.D.
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Journal Title
J Biol.Chem. 280(3)
Pages: 35028-35037
Description
「研究成果報告書概要(欧文)」より
