Bone remodeling signaled by a dihydropyridine-and phenylalkylamine-sensitive calcium channel.

SE Guggino, D Lajeunesse, JA Wagner… - Proceedings of the …, 1989 - pnas.org
SE Guggino, D Lajeunesse, JA Wagner, SH Snyder
Proceedings of the National Academy of Sciences, 1989pnas.org
An osteoblast calcium channel demonstrated by single channel recordings is associated
with calcium antagonist receptor binding sites in osteoblast-like osteosarcoma cells. By
using whole cell current recordings we now show that this channel is stimulated by the
dihydropyridine calcium agonist drug BAY K 8644. A physiological relevance of these
channels is apparent from the stereoselective, potent inhibition of parathyroid hormone-
stimulated calcium uptake into osteoblast-like cells in culture by desmethoxyverapamil, a …
An osteoblast calcium channel demonstrated by single channel recordings is associated with calcium antagonist receptor binding sites in osteoblast-like osteosarcoma cells. By using whole cell current recordings we now show that this channel is stimulated by the dihydropyridine calcium agonist drug BAY K 8644. A physiological relevance of these channels is apparent from the stereoselective, potent inhibition of parathyroid hormone-stimulated calcium uptake into osteoblast-like cells in culture by desmethoxyverapamil, a phenylalkylamine calcium antagonist. Secretion by these cells of the bone matrix protein osteocalcin is stimulated by BAY K 8644 and blocked by desmethoxyverapamil and nitrendipine. Evidence for a role of this channel in bone remodeling in intact animals comes from enhanced bone resorption in fetal rat bones observed with BAY K 8644 and stereoselective, potent blockade of resorption by desmethoxyverapamil.
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