Corticotropin-Releasing Factor Increases Ca(2+)sub i via Receptor- Mediated Ca(2+) Channels in Human Epidermoid A-431 Cells
Abstract
Corticotropin-releasing factor (CRF) has been shown to attenuate vascular leakage in injured skin, mucous membrane, muscle, and brain. Calcium is thought to play an important role in many of the physiological responses to CRF, but there has been little characterization of how calcium is involved in process by which CRF protects damaged tissues. The goal of this study was to characterize changes in cytosolic free calcium concentrations (Ca(2+)sub i) in human epidermoid A-431 cells exposed to human/rat-CRF and to investigate the mechanisms by which these changes occur. The resting (Ca(2+)sub i) in normal cells at 37 deg C was 66 + or - 4 nM (n = 32). When cells were treated with CRF, (Ca(2+)sub i) increased immediately. The increase depended on CRF concentration, with a median effective concentration of 11 pM. This increase in (Ca(2+)sub i) depended on external Ca(2+) but not Na(+), Mg(2+), or K(+). La(3+) (10 microns M) and Co(2+) (10 microns M) inhibited the CRF-induced (Ca(2+)sub i) increase, whereas verapamil and nifedipine tested at concentrations up to 1 mM did not. Alpha-Helical CRF-(9-41), a synthetic CRF receptor antagonist, and pertussis toxin blocked the increase in (Ca(2+)sub i), induced by CRF, which suggests that the entry of extracellular Ca(2+) is mediated by receptor-operated Ca(2+) channels coupled with pertussis toxin-sensitive G proteins.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 1994
- Accession Number
- ADA279920
Entities
People
- Juliann G Kiang
Organizations
- Walter Reed Army Institute of Research