Corticotropin-Releasing Factor Increases Ca(2+)sub i via Receptor- Mediated Ca(2+) Channels in Human Epidermoid A-431 Cells
WALTER REED ARMY INST OF RESEARCH WASHINGTON DC
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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 Ca2sub i in human epidermoid A-431 cells exposed to humanrat-CRF and to investigate the mechanisms by which these changes occur. The resting Ca2sub i in normal cells at 37 deg C was 66 or - 4 nM n 32. When cells were treated with CRF, Ca2sub i increased immediately. The increase depended on CRF concentration, with a median effective concentration of 11 pM. This increase in Ca2sub i depended on external Ca2 but not Na, Mg2, or K. La3 10 microns M and Co2 10 microns M inhibited the CRF-induced Ca2sub 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 Ca2sub i, induced by CRF, which suggests that the entry of extracellular Ca2 is mediated by receptor-operated Ca2 channels coupled with pertussis toxin-sensitive G proteins.