title: Effect of the lectin concanavalin-A on calcium-regulated adenosine 3',5'-monophosphate accumulation in bovine parathyroid cells.
abstract: Extracellular calcium (Ca2+) is the major physiological regulator of parathyroid function; high Ca2+ decreases PTH secretion as well as reduces cAMP accumulation. There is an increasing body of evidence suggesting the presence of a receptor-like mechanism at the surface of the parathyroid cell which mediates these and other actions of Ca2+. In the present studies we used the lectin Concanavalin-A (Con-A) to investigate the possible role of carbohydrate moieties in the regulation of cAMP metabolism by Ca2+ in bovine parathyroid cells, which is thought to involve inhibition of adenylate cyclase via activation of the guanine nucleotide regulatory protein Gi. Pretreatment of parathyroid cells with Con-A for 15-60 min significantly reversed the inhibitory effect of high Ca2+ on dopamine-stimulated cAMP accumulation, reducing the inhibition at 3 mM Ca2+ from 70 +/- 3% to 30 +/- 3%. This effect was also observed in the absence of preincubation and with concentrations of Con-A as low as 40 micrograms/ml and was reversed by alpha-methyl-D-glucoside, a specific antagonist of the lectin. The lectin also reversed the inhibitory effects of Ca2+ (2-3 mM) on cAMP accumulation stimulated by isoproterenol and forskolin to a comparable extent. Prostaglandin F2 alpha-induced inhibition of cAMP accumulation (likewise mediated by Gi) was, however, not reversed by Con-A, suggesting that the lectin did not have a generalized effect on the cell surface or on receptors inhibiting adenylate cyclase. Moreover, fluoride-induced inhibition of cAMP accumulation was not reversed by Con-A, providing additional evidence that the lectin did not act at or distal to Gi (i.e. modulate Gi, adenylate cyclase, and/or phosphodiesterase). The present study suggests that Con-A may modulate the actions of extracellular Ca2+ on parathyroid secretion, possibly modifying the interaction of Ca2+ with the cell surface by affecting carbohydrate moieties that seem to be important in the Ca2(+)-sensing process. The structural element involved in Ca2+ sensing in the parathyroid cell may be a glycoprotein or closely associated with glycoproteins with carbohydrate chains containing alpha-methyl-D-glycoside.
authors.affiliation: Endocrine-Hypertension Unit, Brigham and Women's Hospital, Boston, Massachusetts 02115.
authors.forename: G
authors.initials: G
authors.lastname: el-Hajj Fuleihan
authors.forename: E M
authors.initials: EM
authors.lastname: Brown
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D002417:Cattle; D005576:Colforsin / Q000494:pharmacology; D003208:Concanavalin A / Q000494:pharmacology*; D000242:Cyclic AMP / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015237:Dinoprost / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology; D005459:Fluorides / Q000494:pharmacology; D007477:Ions; D007545:Isoproterenol / Q000494:pharmacology; D008757:Methylglucosides / Q000494:pharmacology; D009994:Osmolar Concentration; D010280:Parathyroid Glands / Q000166:cytology / Q000378:metabolism*
chemical_list: D007477:Ions; D008757:Methylglucosides; D003208:Concanavalin A; D005576:Colforsin; C027020:methylglucoside; D015237:Dinoprost; D000242:Cyclic AMP; D007545:Isoproterenol; D005459:Fluorides; D002118:Calcium; D004298:Dopamine