Inhibition of nNOS expression in the macula densa by COX-2-derived prostaglandin E(2)
| Autor: | Diane Mizel, Alex Paliege, Jurgen Schnermann, Carmen Medina, Yuning G. Huang, Josephine P. Briggs, Anita Pasumarthy, Sebastian Bachmann, Tianxin Yang |
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| Rok vydání: | 2004 |
| Předmět: |
medicine.medical_specialty
Physiology Nitric Oxide Synthase Type I Kidney Plasma renin activity Dinoprostone Renin-Angiotensin System Mice Internal medicine Renin–angiotensin system Renin medicine Animals Prostaglandin E2 reproductive and urinary physiology Regulation of gene expression Mice Knockout biology Juxtaglomerular apparatus Nitric oxide synthase Isoenzymes medicine.anatomical_structure Endocrinology nervous system Gene Expression Regulation Cyclooxygenase 2 Prostaglandin-Endoperoxide Synthases biology.protein Macula densa Nitric Oxide Synthase medicine.drug |
| Zdroj: | American journal of physiology. Renal physiology. 287(1) |
| ISSN: | 1931-857X |
| Popis: | It is well established that cyclooxygenase-2 (COX-2) and the neuronal form of nitric oxide synthase (nNOS) are coexpressed in macula densa cells and that the expression of both enzymes is stimulated in a number of high-renin states. To further explore the role of nNOS and COX-2 in renin secretion, we determined plasma renin activity in mice deficient in nNOS or COX-2. Plasma renin activity was significantly reduced in nNOS −/− mice on a mixed genetic background and in COX-2 −/− mice on either BALB/c or C57/BL6 congenic backgrounds. In additional studies, we accumulated evidence to show an inhibitory influence of PGE2on nNOS expression. In a cultured macula densa cell line, PGE2significantly reduced nNOS mRNA expression, as quantified by real-time RT-PCR. In COX-2 −/− mice, nNOS mRNA expression in the kidney, determined by real-time RT-PCR, was upregulated throughout the postnatal periods, ranging from postnatal day ( PND) 3 to PND 60. The induction of nNOS protein expression and NOS activity in COX-2 −/− mice was localized to macula densa cells using immunohistochemistry and NADPH-diaphorase staining methods, respectively. Therefore, these findings reveal that the absence of either COX-2 or nNOS is associated with suppressed renin secretion. Furthermore, the inhibitory effect of PGE2on nNOS mRNA expression indicates a novel interaction between NO and prostaglandin-mediated pathways of renin regulation. |
| Databáze: | OpenAIRE |
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