Studies on the mechanisms by which 2-chloroadenosine stimulates bone resorption in tissue culture.
The effect of 2-chloroadenosine on bone resorption was studied in calvarial bones from 6-7-day-old mice in organ culture. 2-Chloroadenosine stimulated the mobilization of minerals (40Ca, 45Ca) and increased the degradation of matrix ([3H]proline) from the bones. The nucleoside also caused an increased release of beta-glucuronidase, a lysosomal enzyme. In doses above 30 microM 2-chloroadenosine was cytotoxic, as evidenced by an increased release of lactate dehydrogenase. 2-Chloroadenosine-stimulated resorption could be inhibited by calcitonin, increased concentration of phosphate in culture medium, cortisone, dexamethasone, indomethacin, naproxen, meclofenamic acid and 5,8,11,14-eicosatetraynoic acid. 2-Chloroadenosine was much more sensitive to inhibition by dexamethasone than was parathyroid hormone. The response to the maximal dose of 2-chloroadenosine could not be enhanced by parathyroid hormone, 1 alpha-hydroxyvitamin D-3 and prostaglandin E2. An exposure to 2-chloroadenosine for 12 h was not sufficient to produce prolonged resorption. The results suggest that 2-chloroadenosine stimulated bone resorption by a process which is dependent on osteoclastic activity. The possibility that the effect of 2-chloroadenosine, either directly or indirectly, is related to formation of prostaglandins is discussed in the light of the above data.
D015762:2-Chloroadenosine; D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001862:Bone Resorption / Q000187:drug effects*; D001842:Bone and Bones / Q000378:metabolism; D002117:Calcitriol / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D046508:Culture Techniques; D015232:Dinoprostone; D005966:Glucuronidase / Q000378:metabolism; D051379:Mice; D010281:Parathyroid Hormone / Q000494:pharmacology; D011458:Prostaglandins E / Q000494:pharmacology
D001095:Arachidonic Acids; D010281:Parathyroid Hormone; D011458:Prostaglandins E; D015762:2-Chloroadenosine; D016718:Arachidonic Acid; D005966:Glucuronidase; D002117:Calcitriol; D000241:Adenosine; D015232:Dinoprostone; D002118:Calcium