Impaired rapid mineralocorticoid action on free intracellular calcium in pseudohypoaldosteronism.
Earlier observations on impaired in vitro effects of aldosterone on lymphocytic sodium and potassium pointed to the involvement of a defective nongenomic rather than genomic effector in pseudohypoaldosteronism. In this study, we investigated nongenomic aldosterone action in five patients with pseudohypoaldosteronism with regard to a rapid increase of free intracellular calcium [Ca2+]i in cultured nasal epithelial cells, assumably reflecting calcium influx through calcium channels. Patients were defined by episodes of salt loss despite high plasma aldosterone and renin levels. Four unaffected members of the families and four independent subjects served as controls. Considering an aldosterone-induced increase of [Ca2+]i by at least 10 nm as positive response, only 12% of cells from patients were responsive compared with 25% in normal subjects (P < 0.05). In terms of absolute changes, mean increase of [Ca2+]i was 1.6 +/- 1.1 nm in the patients (range-1-4) and 9.5 +/- 2.7 nm (P < 0.025) in the controls (range 1-25). Basal [Ca2+]i was not different between both groups (167 +/- 5 vs. 169 +/- 8 nm, mean +/- SE). These findings show an impaired nongenomic mineralocorticoid effector in patients with pseudohypoaldosteronism, which is in line with a defective sodium channel as shown recently by molecular cloning, and also with the fact that the classical, genomic intracellular receptor is structurally normal in these patients.
Gamarra
F
F
Institute of Clinical Pharmacology, Faculty of Clinical Medicine at Mannheim, University of Heidelberg, Federal Republic of Germany.
Simic-Schleicher
G
G
Huber
R M
RM
Ulsenheimer
A
A
Scriba
P C
PC
Kuhnle
U
U
Wehling
M
M
D000328:Adult; D000450:Aldosterone / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D016257:Fura-2; D006801:Humans; D007223:Infant; D007425:Intracellular Membranes / Q000378:metabolism*; D008297:Male; D009297:Nasal Mucosa / Q000378:metabolism / Q000473:pathology; D011546:Pseudohypoaldosteronism / Q000378:metabolism*
D000450:Aldosterone; D002118:Calcium; D016257:Fura-2