Adenylate cyclase blockers dissociate PTH-stimulated bone resorption from cAMP production
| Autor: | Ian R. Reid, D. H. Gray, Jillian Cornish, Carolyn Lowe, Stephen J. M. Skinner |
|---|---|
| Rok vydání: | 1990 |
| Předmět: |
DNA Replication
medicine.medical_specialty Osteolysis Physiology Phenylalanine Endocrinology Diabetes and Metabolism Indomethacin Parathyroid hormone In Vitro Techniques Bone and Bones Bone resorption Mice chemistry.chemical_compound Isomerism Theophylline 1-Methyl-3-isobutylxanthine Physiology (medical) Internal medicine Cyclic AMP medicine Animals Bone Resorption Forskolin Adenine Phosphodiesterase medicine.disease Adenosine Resorption Kinetics Endocrinology chemistry Parathyroid Hormone Calcitonin Protein Biosynthesis Adenylyl Cyclase Inhibitors Dideoxyadenosine Calcium medicine.drug |
| Zdroj: | American Journal of Physiology-Endocrinology and Metabolism. 258:E708-E714 |
| ISSN: | 1522-1555 0193-1849 |
| Popis: | It is uncertain whether adenosine 3',5'-cyclic monophosphate (cAMP) or the inositol-calcium pathway mediates the stimulation of bone resorption by parathyroid hormone (PTH). Incubation of bone organ cultures with cAMP analogues and forskolin has not resolved this question because of the cellular inhomogeneity of bone and the consequent presence of adenylate cyclase-linked receptors for both PTH and calcitonin, hormones with opposite effects on bone resorption. We have used two new inhibitors of adenylate cyclase, 9-(tetrahydro-2-furyl)adenine (SQ 22536) and 2',5'-dideoxyadenosine (DDA), to directly reassess the role of cAMP in PTH-stimulated osteolysis. SQ 22536 (0.01-1.0 mM) and DDA (0.01-1.0 mM) completely blocked PTH stimulation of cAMP production measured in the absence of a phosphodiesterase blocker. In the presence of 1 mM 3-isobutyl-1-methylxanthine, half-maximal inhibition of PTH-induced cAMP production occurred with 0.2 mM SQ and 0.1 mM DDA, respectively. These concentrations of SQ and DDA had no effect on PTH-stimulated 45Ca release from calvaria, although both agents inhibited bone resorption when present at concentrations of 1-2 mM. At these levels, SQ and DDA caused equivalent inhibition of 45Ca release stimulated by 1,25-dihydroxyvitamin D3 but did not affect basal 45Ca release or [3H]-phenylalanine incorporation. It is concluded that substantial blockade of PTH-induced cAMP production does not affect this hormone's stimulation of bone resorption, which is therefore likely to be mediated by another intracellular messenger system, possibly calcium. In millimolar concentrations, SQ and DDA appear to be nonspecific blockers of osteoclastic bone resorption. |
| Databáze: | OpenAIRE |
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