Comparative study on the effect of calcium channel blockers on basal and parathyroid hormone-induced bone resorption in vitro.
A number of clinical and experimental studies suggest that the effects of calcium channel blockers are not limited to the cardiovascular system but might also involve skeletal calcium metabolism due to the presence of L-type calcium channels in osteoblastic cells. We therefore investigated the influence of calcium channel blockers of the dihydropyridine type (nifedipine, amlodipine) as well as of the phenylalkylamine type (verapamil, gallopamil) on basal and parathyroid hormone-induced bone resorption utilizing organ-cultured neonatal mouse calvaria. Only at 10(-4) M, amlodipine, verapamil and gallopamil reduced basal and parathyroid hormone-induced resorption In contrast, nifedipine, between 10(-5)-10(-4) M, exhibited a dose-dependent inhibitory effect on parathyroid hormone-related bone resorption by up to 50%. When calvariae were cultured for 48 hr in the presence of inhibitory concentrations of the calcium channel blockers and then stimulated with parathyroid hormone, only parietal bones pretreated with nifedipine remained completely responsive to the bone resorbing action of the hormone.
Redlich
K
K
Department of General and Experimental Pathology, University of Vienna Medical School, Wien, Austria.
Pietschmann
P
P
Stulc
T
T
Peterlik
M
M
D017311:Amlodipine / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001862:Bone Resorption / Q000139:chemically induced / Q000188:drug therapy*; D002121:Calcium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D005711:Gallopamil / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D009543:Nifedipine / Q000494:pharmacology / Q000627:therapeutic use; D009924:Organ Culture Techniques; D010281:Parathyroid Hormone / Q000009:adverse effects*; D010294:Parietal Bone / Q000166:cytology / Q000187:drug effects; D013047:Specific Pathogen-Free Organisms; D014700:Verapamil / Q000494:pharmacology / Q000627:therapeutic use
D002121:Calcium Channel Blockers; D010281:Parathyroid Hormone; D017311:Amlodipine; D005711:Gallopamil; D014700:Verapamil; D009543:Nifedipine