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.
el-Hajj Fuleihan
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Endocrine-Hypertension Unit, Brigham and Women's Hospital, Boston, Massachusetts 02115.
Katz
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Kifor
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Gleason
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Brown
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D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002413:Cations, Divalent / Q000494:pharmacology; D002417:Cattle; D003208:Concanavalin A / Q000494:pharmacology*; D003600:Cytosol / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism*; D007295:Inositol Phosphates / Q000378:metabolism; D009994:Osmolar Concentration; D010280:Parathyroid Glands / Q000166:cytology / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000378:metabolism*; D015290:Second Messenger Systems
D002413:Cations, Divalent; D007295:Inositol Phosphates; D010281:Parathyroid Hormone; D003208:Concanavalin A; D002118:Calcium