Modulation of buccal mucosal calcium channel activity by salivary mucins.
The effect salivary mucus glycoproteins on the activity of calcium channel isolated from buccal mucosal cell membranes was investigated. The channel complex following reconstitution into phospholipid vesicles exhibited an active 45Ca2+ uptake and responded to calcium channel activator, BAY K8644, and the antagonist, PN200-110. The uptake of 45Ca2+, while only moderately (15%) affected by the intact mucus glycoprotein was significantly inhibited (60-64%) by the acidic mucus glycoprotein fractions. This effect was associated with the sialic acid and sulfate ester groups of the carbohydrate chains. The channel complex in the presence of epidermal growth factor (EGF) and ATP responded by an increase in protein tyrosine phosphorylation of 55 and 170kDa proteins, and the vesicles containing the phosphorylated channels showed a 46% increase in 45Ca2+ uptake. The phosphorylation and the calcium uptake were susceptible to inhibition by a specific tyrosine kinase inhibitor, genistein. The binding of EGF to buccal mucosal calcium channel receptor protein was also inhibited (36-41%) by acidic mucus glycoprotein. The reduction in binding was dependent upon the presence of sulfate ester and sialic acid groups, as evidenced by the loss of the glycoprotein inhibitory capacity following removal of these groups. The results for the first time demonstrate that salivary mucins actively participate in the modulation of the buccal mucosal calcium channel activity, a process of importance to the preservation of soft oral integrity.
Slomiany
B L
BL
Research Center New Jersey Dental School, University of Medicine and Dentistry of New Jersey, Newark.
Fekete
Z
Z
Murty
V L
VL
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 / Q000502:physiology*; D002610:Cheek; D004815:Epidermal Growth Factor / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D017275:Isradipine / Q000494:pharmacology; D008297:Male; D009061:Mouth Mucosa / Q000187:drug effects / Q000378:metabolism*; D009077:Mucins / Q000494:pharmacology*; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012471:Salivary Proteins and Peptides / Q000494:pharmacology*
D015220:Calcium Channels; D009077:Mucins; D012471:Salivary Proteins and Peptides; 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