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

S. E. Guggino, D. Lajeunesse, J. A. Wagner, S. H. Snyder

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2957-2960
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Volume86
Issue number8
DOIs
StatePublished - 1989

ASJC Scopus subject areas

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