GM1-ganglioside regulation of EGF-induced gastric mucosal calcium channel activation.
1. Calcium channels, isolated from gastric epithelial cell membranes when reconstituted into phosphatidylcholine vesicles exhibited active 45Ca2+ uptake as evidenced by a dose dependent response to calcium channel activator, BAY K8644, and antagonist, PN200-110. 2. The channels on epidermal growth factor (EGF) binding in the presence of ATP showed an increase in tyrosine phosphorylation of 55 and 170 kDa calcium channel proteins. Such phosphorylated channels following reconstitution into the vesicles displayed a 48% greater 45Ca2+ uptake than that of the controls. 3. The binding of EGF to calcium channel protein was inhibited by GM1-ganglioside reaching maximum inhibition of 65% at 40 nM GM1. In contrast, calcium channel antagonist, PN200-110, had no effect on EGF binding. 4. The EGF-stimulated calcium channel protein phosphorylation was inhibited by GM1. This inhibitory effect was mainly reflected in the decrease of tyrosine phosphorylation of 55 and 170 kDa proteins. 5. The results suggest the participation of GM1-ganglioside in the regulation of EGF-stimulated gastric mucosal calcium channel activation.
Slomiany
B L
BL
Research Center, New Jersey Dental School, University of Medicine and Dentistry of New Jersey, Newark 07103-2400.
Liu
J
J
Yao
P
P
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; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005677:G(M1) Ganglioside / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D017275:Isradipine / Q000494:pharmacology; D008297:Male; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002135:Calcium-Binding Proteins; D005677:G(M1) Ganglioside; 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