V. Zusammenfassung und Abstract
V.2. Abstract
Zusammenfassung und Abstract 74
-/-Zusammenfassung und Abstract 75 mice. Astonishingly, a significant β subunit decrease of EP4-receptor-/- mice could be noticed whereas the γ-subunit expression remained stable.
It is postulated that there is an increased water and salt loss caused by the deficit or the inhibition of NKCC2 or ROMK which leads to inadequate ability for urine to concentrate in the thick ascending limb of Henle. Furthermore, it is suspected that, for the same reason, the expression of COX-2 and renin in the juxtaglomerular apparatus is increased by a decreased chloride concentration. If the already decreased or inhibited exprimated channels were additionally downregulated by COX-2, as could be supposed according to the previous results, there would be a circulus vitiosus of decreased channel concentration Æ increased COX-2 concentration Æ decreased channel concentration, which could be interrupted by the administering of a COX-2 inhibitor.
The results also permit a further assumption: Besides the already known mechanism of regulation by increased renin, which leads to an increased α-ENaC concentration by RAAS, β- and γ-subunits seem to be simultaneously upregulated to this. This mechanism is probably regulated by Cyclooxygenase-2 and the receptor EP4 for ENaC γ. Cyclooxygenase-1, which is, like ENaC, also strongly exprimated in the collecting duct, could be responsible for the increased PGE2 which, perhaps via EP4 as well, leads to an increase of ENaC β. This mechanism was not investigated in this essay. According to that thesis, the three subunits would be simultaneously up-regulated which would cause a stronger effect, although this would be achieved by different mechanisms.
It should be considered, that salt and water loss is only decreased by the processes in the collecting duct. The reason for this is that a big part of the urine concentration takes place in the thick ascending limb of Henle, where a defect or inhibited channel does not allow the exhaustion of the full potential of concentration.
In order to investigate this hypothesis further, more experiments would be necessary that base on the present examination, which, apart from the mRNA concentration, measure protein concentration and channel activities as well.
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Anhang
VII. Anhang
Verzeichnis der akademischen Lehrer
Meine akademischen Lehrer waren die Damen und Herren:
In Marburg: Aumüller, Adamkiewicz, Barth, Basler, Baum, Becker, Behr, Bertalanffy, Bien, Christiansen, Cetin, Czubayko, Daut, Eilers, Feuser, Fuchs, Gerdes, Geus, Gotzen, Gress, Griss, Grzeschik, Gudermann, Hasilik, Hertl, Hofmann, Jungclas, Kann, Kill, Klenk, Klose, Koolman, Krause, Kretschmer, Krieg, Kroll, Lang, Langer, Lill, Löffler, Maier, Maisch, Mandrek, Moll, Moosdorf, Müller, Mueller, Mutters, Neubauer, Nüsing, Oertel, Remschmidt, Renz, Röhm, Rothmund, Schäfer, Schmidt, Schnabel, Schuhmacher, Seitz, Seyberth, Steiniger, Stiletto, Studer, Vogelmeier, Voigt, Wagner, Weihe, Werner, Wulf
In Kassel Siebert und in London (St. Helier) Bending