REGULATION OF BUCCAL MUCOSAL CALCIUM-CHANNEL ACTIVITY BY SALIVARY MUCINS

1. The effect salivary mucins on the activity of calcium channel isola ted from buccal mucosal cell membranes was investigated. The uptake of Ca-45(2+) while only moderately (15%) affected by the intact low and high molecular weight mucin forms, was significantly inhibited, by the acidic low and high molecular weight salivary mucins which evoked 64 and 60% inhibition, respectively. 2. The inhibitory effect of salivary mucins was associated with the sialic acid and sulfate ester groups o f the carbohydrate chains, as the removal of either group caused parti al loss in the glycoproteins inhibition, and the complete loss in the inhibitory effect occurred following desialylation and desulfation. 3. The channel in the presence of epidermal growth factor (EGF) and ATP responded by an increase in tyrosine phosphorylation of 55 and 170 kDa proteins, and the phosphorylated channels showed a 46% increase in Ca -45(2+) uptake. The phosphorylation and the calcium uptake were suscep tible to inhibition by a specific tyrosine kinase inhibitor, genistein . 4. The binding of EGF to calcium channel receptor protein was inhibi ted by the low and high molecular weight acidic mucins, causing 41.2 a nd 36.1% reduction, respectively. This reduction in binding was depend ent upon the presence of sulfate ester and sialic acid groups, as evid enced by the loss of the glycoproteins' inhibitory capacity following removal of these groups. 5. The results for the first time demonstrate that salivary mucins actively participate in the modulation of the EG F-controlled buccal mucosal calcium channel activity expression, a pro cess of importance to the preservation of oral tissue integrity.