Effect of sucralfate on gastric mucosal calcium channels activity.
1. The effect of anti-ulcer agent, sucralfate, on the activity of the gastric mucosal calcium channel was investigated using calcium channels purified from rat gastric epithelial cell membranes. 2. The channels on reconstitution into phosphatidylcholine vesicles responded in a concentration-dependent manner to a calcium channel activator, BAY K8644, as well as to a calcium channel antagonist, PN200-110. The 45Ca2+ uptake was inhibited by sucralfate. Maximum inhibitory effect was attained at 100 micrograms/ml sucralfate, at which point a 52% decrease in the uptake occurred. 3. EGF-induced channel protein phosphorylation showed an increase in tyrosine phosphorylation of 55 and 170 kDa proteins, and the vesicles containing the phosphorylated channels displayed a 48% greater 45Ca2+ uptake. This phosphorylation process was inhibited by sucralfate. Furthermore, sucralfate also interfered with the binding of EGF to calcium channel protein. 4. The results indicate that sucralfate protects the cellular integrity from calcium imbalance by modulating the EGF-stimulated gastric mucosal calcium channel phosphorylation.
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D002132:Calcium Radioisotopes; D004815:Epidermal Growth Factor / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D017275:Isradipine / Q000494:pharmacology; D008297:Male; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013392:Sucralfate / Q000494:pharmacology*
D015220:Calcium Channels; D002132:Calcium Radioisotopes; D007457:Iodine Radioisotopes; D013392:Sucralfate; D004815:Epidermal Growth Factor; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D017275:Isradipine