Extra- and intracellular potassium concentration and prostaglandin production of skin fibroblasts grown from patients with Bartter's syndrome.
In studies on human skin fibroblasts originating from three patients with Bartter's syndrome and in corresponding age and sex matched controls, the bradykinin stimulated release of PGE2, PGI2, PGF2 alpha and of arachidonic acid was examined. The studies were aimed at demonstrating the possible changes of prostaglandin production under the influence of changing extracellular potassium concentrations (0-12 mmol K/l) in the two study groups. Earlier studies were confirmed and extended by one more pair of fibroblast cultures, showing a decreased bradykinin stimulated PGE2 production in fibroblasts from patients with Bartter's syndrome as compared to control. The difference in bradykinin stimulated PGE2 production was significant, irrespective of the extracellular potassium concentrations, to which the cultures were exposed. The bradykinin stimulated PGE2 and PGF2 alpha-production by control fibroblasts was directly proportional to extracellular potassium concentrations, whereas the PG-production of Bartter's syndrome fibroblasts remained uninfluenced by extracellular potassium. Extra- and intracellular potassium concentrations were directly proportional and there was no difference in this relationship between controls and Bartter's syndrome. The direct proportionality between bradykinin stimulated PGE2 production and potassium concentrations in control fibroblasts is, despite the apparent contradiction, in accordance with findings in the literature. The lack of a comparable proportionality in fibroblasts from patients with Bartter's syndrome is interpreted to correspond to an insensitivity to changes of potassium concentrations and thus to an insensitivity to one of the modulators of AA metabolism.
Barth
A
A
Fanzun
C
C
Lüthy
C
C
Siegrist
M
M
Koegel
R
R
Oetliker
O
O
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000328:Adult; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000096:biosynthesis; D001477:Bartter Syndrome / Q000378:metabolism*; D001920:Bradykinin / Q000494:pharmacology; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D015237:Dinoprost; D015232:Dinoprostone; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006929:Hyperaldosteronism / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D011188:Potassium / Q000378:metabolism* / Q000494:pharmacology; D011453:Prostaglandins / Q000096:biosynthesis*; D011458:Prostaglandins E / Q000096:biosynthesis; D011460:Prostaglandins F / Q000096:biosynthesis; D012016:Reference Values; D012867:Skin / Q000187:drug effects / Q000378:metabolism*
D001095:Arachidonic Acids; D011453:Prostaglandins; D011458:Prostaglandins E; D011460:Prostaglandins F; D016718:Arachidonic Acid; D015121:6-Ketoprostaglandin F1 alpha; D015237:Dinoprost; D015232:Dinoprostone; D011188:Potassium; D001920:Bradykinin