Mucus glycoprotein regulation of gastric mucosal calcium channel activity.
The effect of gastric mucin on the activity of calcium channel isolated from gastric epithelial cell membrane was investigated. The uptake of 45Ca2+ into the vesicle-reconstituted channels, while only moderately (14%) affected by the intact glycoprotein, was found significantly inhibited (59%) by the acidic glycoprotein fraction. This effect was associated with the sialic acid and sulfate ester groups of the glycoprotein. The channel complex in the presence of epidermal growth factor (EGF) and ATP responded by an increase in protein tyrosine phosphorylation, and the vesicles containing the phosphorylated channels showed a 50% increase in 45Ca2+ uptake. The channel protein phosphorylation was inhibited by the acidic mucus glycoprotein, which also interfered with the binding of EGF to the channel protein. The inhibitory effect was dependent upon the presence of sulfate ester and sialic acid groups, and the loss of the inhibitory capacity occurred following their removal. The results indicate that the acidic gastric mucins, by modulating the EGF-controlled calcium channel phosphorylation, play a major role in gastric mucosal calcium homeostasis.
Slomiany
B L
BL
Research Center, New Jersey Dental School, University of Medicine and Dentistry of New Jersey, Newark 07103-2400.
Liu
J
J
Grabska
M
M
Slomiany
A
A
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000378:metabolism / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000166:cytology / Q000502:physiology*; D006801:Humans; D009077:Mucins / Q000502:physiology*; D010766:Phosphorylation; D051381:Rats; D014443:Tyrosine / Q000378:metabolism
D015220:Calcium Channels; D009077:Mucins; D014443:Tyrosine; D004815:Epidermal Growth Factor; D000255:Adenosine Triphosphate; D002118:Calcium