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Leading symptoms of the Hyperprostaglandine-E-Syndrome are an excessive loss of salt and water, an increased production of renine and prostaglandines, a hypercalciurie and a hypertrophie of the juxtaglomerular apparatus. Already prenatal accrues a fetal polyuria and that is why a polyhydramnion can occur. This is the reason for the premature birth between the 28th and 34th gestation week.
The extensive increased renal excretion of prostaglandine E2 is to be held responsible for the clinical symptomes like thirst, fever and growth delay.
In this study we analysed the regulation of the synthesis of the prostaglandines and the influence of electrolytes in primary cultivated cells of the thick ascending limb (m-TAL) of pigs.
After stimulation with hypotonic solution we could announce an increase of prostaglandine E2, of the mPGES-1 mRNA (prostaglandine synthase), the COX-1 and COX-2 mRNA and an increase of the protein of the COX-2.
Which kind of change in the electrolytes is responsible therefore, especially if the deprivation of chloride is the main factor, has to be under examination in more experiments.
After stimulation with isoosmolar solution we could also show an expression of the PGES-1, certainly lesser then after stimulation with hypoosmolar solution. Therefore you can suppose an involvement of the PGES-1 on the synthesis of PGE2 if the salt balance changes.
The results give grounds to believe that the increase of the synthesis of prostaglandines is controlled by MAP kinase.
For more precise answers concerning the involved factors and mechanism of action more experiments need to follow.
The clinical pertinence of more studies become clear if you mind that the only treatment approach of the salt-losing tubulopathies is the inhibition of the synthesis of prostaglandines.
More perceptions about the balance of COX-1/COX-2 in the human body are missing, which are necessary to develop novel therapies.
With the new cell model we could outline first regulatory mechanisms, it seems to be also suitable to analyze more processes.