Modulation of gastric mucosal calcium channels activity by platelet-derived growth factor.
A dihydropyridine-sensitive gastric mucosal calcium channels were isolated from the solubilized epithelial cell membranes by affinity chromatography on wheat germ agglutinin. The channels following labeling the calcium antagonist receptor site with [3H]PN200-100 were reconstituted into phospholipid vesicles which exhibited active 45Ca2+ uptake as evidenced by La3+ displacement assays. The uptake of calcium was independent of sodium and potassium gradients indicating the electroneutral nature of the process. The channels responded in a dose dependent manner to dihydropyridine calcium antagonist, PN200-110, which at 0.5 microns exerted maximal inhibitory affect of 66% on 45Ca2+ uptake, while a 52% enhacement in 45Ca2+ uptake occurred with a specific calcium channel activator, BAY K8644. On platelet-derived growth factor (PDGF) binding in the presence of ATP, channel protein showed an increase in tyrosine phosphorylation of 55 and 170 kDa calcium channel proteins. Such phosphorylated channels following reconstitution into vesicles displayed a 78% greater 45Ca2+ uptake. The results demonstrate the importance of PDGF in the regulation of gastric mucosal calcium uptake.
Slomiany
B L
BL
New Jersey Dental School, University of Medicine and Dentistry of New Jersey, Newark.
Liu
J
J
Fekete
Z
Z
Piotrowski
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*; D002132:Calcium Radioisotopes; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D005753:Gastric Mucosa / Q000166:cytology / Q000378:metabolism*; D066298:In Vitro Techniques; D017275:Isradipine / Q000494:pharmacology; D008297:Male; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D015220:Calcium Channels; D002132:Calcium Radioisotopes; D010982:Platelet-Derived Growth Factor; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D002118:Calcium; D017275:Isradipine