The calcium channel blocker diltiazem lowers serum parathyroid hormone levels in vivo and in vitro.
PTH secretion is inversely related to the extracellular and cytosolic calcium (Ca2+) concentrations and, therefore, might be affected by calcium channel blockers such as diltiazem. To investigate the effects of diltiazem on parathyroid function in vivo, 15 subjects were treated with diltiazem (120-360 mg/day), and 15 subjects were treated with the nonspecific vasodilator hydralazine (75-150 mg/day). Diltiazem lowered serum PTH levels from 1.07 +/- 0.07 to 0.87 +/- 0.07 pg/L (P = 0.001), and increased urinary calcium and decreased urinary phosphate excretion (P less than 0.001 and P less than 0.01, respectively). The hydralazine-treated subjects had no significant differences in any of these parameters. To investigate this effect further, dispersed bovine parathyroid cells were incubated for 2 h with or without diltiazem. Regression analysis of PTH released vs. the concentration of diltiazem (10(-7)-10(-4) mol/L) revealed a significant negative relationship (P less than 0.01) with 40% inhibition of PTH release at 10(-4) mol/L (P less than 0.01). The cytosolic Ca2+ concentration, measured using the Ca2+-sensitive fluorescent dye fura-2, was significantly increased in the presence of 10(-4) mol/L diltiazem (P less than 0.01). In summary, diltiazem lowered PTH levels in vivo and in vitro, perhaps acting as a Ca2+ channel agonist in the parathyroid cell and inhibiting PTH release through a rise in the cytosolic Ca2+ concentration.
Seely
E W
EW
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115.
LeBoff
M S
MS
Brown
E M
EM
Chen
C
C
Posillico
J T
JT
Hollenberg
N K
NK
Williams
G H
GH
D000328:Adult; D000368:Aged; D000818:Animals; D001572:Benzofurans / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002417:Cattle; D003600:Cytosol / Q000378:metabolism*; D004110:Diltiazem / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D016257:Fura-2; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D010280:Parathyroid Glands / Q000187:drug effects / Q000378:metabolism; D010281:Parathyroid Hormone / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism
D001572:Benzofurans; D002121:Calcium Channel Blockers; D010281:Parathyroid Hormone; D010710:Phosphates; D004110:Diltiazem; D016257:Fura-2