EFFECT OF THE LECTIN CONCANAVALIN-A ON CALCIUM-REGULATED ADENOSINE-3',5'-MONOPHOSPHATE ACCUMULATION IN BOVINE PARATHYROID CELLS

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 μg/ml and was reversed by α-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 F2α-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 moieities 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 α-methyl-D-glycoside. © 1990 by The Endocrine Society.