DIFFERENCES IN THE ACTIONS OF CALCIUM VERSUS LANTHANUM TO INFLUENCE PARATHYROID-HORMONE RELEASE

PTH release from bovine parathyroid cells is inhibited by increasing concentrations of extracellular calcium (Ca2+). We have proposed that this inhibition is mediated by Ca2+channels via a G-protein. To further test this hypothesis, we evaluated the effect of lanthanum (La3+), a potent Ca2+channel antagonist that does not cross the cell membrane. PTH release was determined in dispersed bovine parathyroid cells by radioimmunoassay: Extracellular Ca2+concentration was 0.2 mM. PTH release was inhibited by maximal concentrations of La3+to a greater extent than by Ca2+: 93% inhibition by La3+us. 40% by Ca2+. La3+was more potent (set-point = 0.12 mM) than Ca2+(set-point = 1.2 mM). Incubation of parathyroid cells with pertussis toxin, which inactivates a G-protein(s) and blocks inhibition by Ca2+, did not block the inhibition of PTH release by La3+at the concentrations tested. The Ca2+ionophore A23187, which potentiates the effect of Ca2+, did not enhance the inhibition of PTH release by La3+. Increasing concentrations of calcium enhanced the inhibition of PTH release by the Ca2+channel agonist, (+)202-791. The Ca2+channel antagonist, (-)202-791, shifted the Ca2+inhibition curve to the right. La3+did not alter the inhibition of PTH release by the Ca2+channel agonist but blocked the stimulatory effect of the Ca2+channel antagonist, (-)202-791. In summary: 1) La3+, which blocks Ca2+channels and does not cross cell membranes, effects a greater inhibition of PTH release than Ca2+; 2) La3+, like Ca2+, overrides the effect of Ca2+channel antagonist (-)202-791; and 3) La3+, unlike Ca2+, inhibits PTH release by a mechanism that is independent of a pertussis toxin-sensitive G-protein. There may be two cell surface sites that recognize La3+and Ca2+independently. © 1990 by The Endocrine Society.