Intracellular calcium signalling and vascular reactivity in Bartter's syndrome.
We investigated patients affected by Bartter's syndrome in the attempt to localize the intracellular defect mediating the reduced intracellular Ca2+ mobilization that may be responsible for the decreased vascular reactivity characteristic of Bartter's syndrome. Using the formylmethionyl-leucyl-phenylalanine (fMLP) receptor system, which causes, intracellular calcium release, we investigated fMLP-stimulated intracellular inositol 1,4,5-trisphosphate (IP3) production as well as the number and affinity of fMLP receptors in neutrophils from Bartter's syndrome patients and healthy controls. Scatchard plot analysis of radioactive fMLP binding to neutrophils indicated that there were no differences in either cell receptor number and affinity for ligand between healthy controls (n = 5) and patients with Bartter's syndrome (n = 5): 6,151 +/- 1,431 vs. 7,112 +/- 2,566 receptors/cell; K(D): 0.446 +/- 0.14 vs. 0.454 +/- 0.09 pM of fMLP. 5- and 10-second fMLP-stimulated intracellular IP3 production was instead reduced in patients affected by Bartter's syndrome: 2.479 +/- 1.07 vs. 4.073 +/- 1.04 nmol/10(7) cells at 5 s (n = 8; p < 0.01); 1.673 +/- 0.741 vs. 3.766 +/- 1.348 nmol/10(7) cells at 10 s (n = 8; p < 0.005). The results of this study indicate that the anomaly of intracellular calcium mobilization in patients with Bartter's syndrome arises from a defect at the postreceptor level. The anomalous calcium signalling that takes place in Bartter's syndrome may provide a mechanism for the hyporesponsiveness to pressor stimuli characteristic of these patients.
Calò
L
L
Department of Internal Medicine, University of Padova, Italy.
D'Angelo
A
A
Cantaro
S
S
Rizzolo
M
M
Favaro
S
S
Antonello
A
A
Borsatti
A
A
D000328:Adult; D001477:Bartter Syndrome / Q000503:physiopathology*; D001808:Blood Vessels / Q000503:physiopathology*; D002118:Calcium / Q000502:physiology*; D005260:Female; D006801:Humans; D007293:Inosine Triphosphate / Q000096:biosynthesis; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000378:metabolism; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000378:metabolism; D018000:Receptors, Peptide / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D018000:Receptors, Peptide; D007293:Inosine Triphosphate; D009240:N-Formylmethionine Leucyl-Phenylalanine; D002118:Calcium