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+ vs. 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.
Fitzpatrick
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University of Texas Health Science Center, San Antonio.
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers; D002417:Cattle; D066298:In Vitro Techniques; D007700:Kinetics; D007811:Lanthanum / Q000494:pharmacology*; D009539:Nicotinic Acids / Q000494:pharmacology; D010069:Oxadiazoles; D010280:Parathyroid Glands / Q000187:drug effects / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000378:metabolism*; D037342:Pertussis Toxin; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D009539:Nicotinic Acids; D010069:Oxadiazoles; D010281:Parathyroid Hormone; D010566:Virulence Factors, Bordetella; C049834:PN 202-791; D000001:Calcimycin; D007811:Lanthanum; D037342:Pertussis Toxin; D002118:Calcium