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Calmodulin increases the sensitivity of type 3 inositol-1,4, 5-trisphosphate receptors to Ca(2+) inhibition in human bronchial mucosal cells.
- Source :
- Molecular Pharmacology; March 2000, Vol. 57 Issue: 3 p564-7, 4p
- Publication Year :
- 2000
-
Abstract
- Inositol-1,4,5-trisphosphate (IP(3)) releases Ca(2+) from intracellular stores by binding to its receptor (IP(3)R), a multigene family of Ca(2+)-release channels consisting of IP(3)R1, IP(3)R2, and IP(3)R3. IP(3)R1 is stimulated by low cytoplasmic Ca(2+) concentrations and inhibited by high concentrations. Discrepant reports appeared about the effect of cytoplasmic Ca(2+) on IP(3)R3, showing either a bell-shaped dependence or only a stimulatory phase with no negative feedback by high Ca(2+) concentrations. We investigated how calmodulin interfered with the feedback of cytosolic Ca(2+) on the unidirectional IP(3)-induced Ca(2+) release in permeabilized 16HBE14o- bronchial mucosal cells, where IP(3)R3 represents 93% of the receptors at the mRNA level and 81% at the protein level. Calmodulin inhibited the Ca(2+) release induced by 1.5 microM IP(3) with an IC(50) value of 9 microM. This inhibition was absolutely dependent on the presence of cytosolic Ca(2+). Ca(2+) inhibited the IP(3)R with an IC(50) value of 0.92 microM Ca(2+) in the absence of calmodulin and with an IC(50) value of 0.15 microM Ca(2+) in its presence. It is concluded that: 1) IP(3)R3 can be inhibited by calmodulin, 2) IP(3)R3 is inhibited by high Ca(2+) concentrations, and 3) calmodulin shifts the inhibitory part of the Ca(2+)-response curve toward lower Ca(2+) concentrations.
Details
- Language :
- English
- ISSN :
- 0026895X and 15210111
- Volume :
- 57
- Issue :
- 3
- Database :
- Supplemental Index
- Journal :
- Molecular Pharmacology
- Publication Type :
- Periodical
- Accession number :
- ejs5550924