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PMID: 2468165 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

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

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 86 ·No. 8 ·1989-04-00 ·Pages 2957-60

Guggino SE, Lajeunesse D, Wagner JA, Snyder SH

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.

MeSH Terms
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester/pharmacology Animals Bone Development Bone Resorption/drug effects Calcium/physiology Calcium Channels/drug effects,physiology Calcium-Binding Proteins/metabolism Cells, Cultured Dihydropyridines/pharmacology Electric Conductivity Osteoblasts/physiology Osteocalcin Parathyroid Hormone/pharmacology Rats Receptors, Nicotinic/physiology Stereoisomerism
Chemicals
Calcium Channels Calcium-Binding Proteins Dihydropyridines Parathyroid Hormone Receptors, Nicotinic Osteocalcin 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester Calcium
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Guggino S E
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Lajeunesse D
Wagner J A
Snyder S H
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26 references, click to expand
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.86.8.2957
Published
1989-04-00
Pages
2957-60
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC287039
Subset
IM
Grants
NIDA NIH HHS · DA-00074 · United States
NIMH NIH HHS · MH-18501 · United States
NINDS NIH HHS · NS-16375 · United States
External Links
PubMed source DOI: 10.1073/pnas.86.8.2957 PMC Full Text View journal details
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