Modulation of gastric mucosal calcium channel activity by sucralfate.
A gastric mucosal calcium channel complex was isolated from solubilized epithelial cell membranes by affinity chromatography on wheat germ agglutinin. The complex following reconstitution into phosphatidylcholine vesicles exhibited an active 45Ca2+ uptake and responded to calcium channel activator, BAY K8644, and the antagonist, PN200-110. The uptake of 45Ca2+ was inhibited by an antiulcer agent, sucralfate, which at 100 micrograms/ml evoked maximal inhibitory effect of 52%. The channel complex on epidermal growth factor (EGF) binding in the presence of ATP showed an increase in tyrosine phosphorylation of 55 and 170kDa proteins, and the vesicles containing the phosphorylated channels displayed a 48% greater 45Ca2+ uptake. The phosphorylation process was inhibited by sucralfate, which also interfered with the binding of EGF to calcium channel protein. The results indicate that sucralfate has the ability to protect the cellular integrity from calcium imbalance.
Slomiany
B L
BL
Research Center, New Jersey Dental School, University of Medicine and Dentistry of New Jersey, Newark 07103-2400.
Liu
J
J
Slomiany
A
A
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D017275:Isradipine / Q000494:pharmacology; D010766:Phosphorylation; D051381:Rats; D013392:Sucralfate / Q000494:pharmacology*; D014443:Tyrosine / Q000378:metabolism
D015220:Calcium Channels; D014443:Tyrosine; D013392:Sucralfate; D004815:Epidermal Growth Factor; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D002118:Calcium; D017275:Isradipine