Effects of the lectin concanavalin-A on the regulation of second messengers and parathyroid hormone release by extracellular Ca2+ in bovine parathyroid cells.

The lectin Concanavalin-A (Con-A) binds to cell surface carbohydrate-containing moieties and modulates the function of a variety of glycoprotein receptors. Since extracellular calcium (Ca2+) may regulate parathyroid function by a receptor-like process, we examined the effects of Con-A on various aspects of Ca(2+)-regulated parathyroid function. We recently showed that Con-A significantly reduces the inhibitory effects of high Ca2+ on dopamine as well as isoproterenol- and forskolin-stimulated cAMP accumulation. In our present studies Con-A similarly reduced the inhibitory effect of 2.0 mM Ca2+ on PTH release from 60 +/- 6% to 40 +/- 6% and increased the set-point for Ca(2+)-regulated PTH release from 1.25 to 1.8 mM. This effect was dose dependent. Con-A also inhibited the Ca(2+)-stimulated accumulation of inositol phosphates by 50-60% in association with a marked reduction in the high Mg(2+)-evoked spike in cytosolic Ca2+ as well as a significant decrease in the sustained rise in cytosolic Ca2+ at 2-3 mM extracellular Ca2+. These data provide further evidence for a key role for cell surface carbohydrate-containing moieties in the mechanism through which parathyroid cells "sense" Ca2+ and, in turn, regulate PTH release, phosphoinositide turnover, and the release of intracellular Ca2+ stores. It is possible that the putative Ca2+ receptor is a glycoprotein or is closely associated with glycoproteins or other moieties containing alpha-methyl-D-glucoside or alpha-methyl-D-mannoside residues.