ISSN:
1573-4935
Keywords:
cystic fibrosis
;
chloride transport
;
exocytosis
;
calcium
;
calmodulin
;
B-adrenergic
;
cyclic AMP
Source:
Springer Online Journal Archives 1860-2000
Topics:
Biology
,
Chemistry and Pharmacology
Notes:
Abstract A biochemical link is proposed between recent observations on defective regulation of Cl− transport in CF respiratory epithelial cells and studies showing altered biological activity of calmodulin in exocrine glands from CF patients. A consensus is emerging that defective β-adrenergic secretory responsiveness in CF cells is caused by a defect in a regulator protein at a site distal to cyclic AMP formation. Our results indicate that this protein might be a specific calmodulin acceptor protein which modifies the activity of calmodulin in epithelial cells. Alteration in Ca2+/calmodulin dependent regulation of Cl− transport and protein secretion could explain (i) alterations in Ca2+ homeostasis seen in CF, (ii) defective β-adrenergic responses of CF cells, and (iii) the observed inability of cyclic AMP (acting via its specific protein kinase, A-kinase) to open apical membrane Cl− channels in CF epithelial cells. Most of the physiological abnormalities of CF including elevated sweat electrolytes and hyperviscous mucus can be explained on this basis.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF01128969
