The effect of prostaglandin I2 and 6a-Carba-PGI2 on the motility of isolated osteoclasts.
We have recently found that calcitonin (CT), a hormone which inhibits osteoclastic bone resorption, completely abolishes the normally intense cytoplasmic movement of isolated osteoclasts. We have also found that prostaglandin (PG)I2 causes an identical change in behaviour. In this paper we extend our investigations into the mode of action of PGI2 and a stable analogue, 6a-Carba-PGI2. We found that, unlike CT which causes prolonged immotility in osteoclasts, the effect of PGI2 and 6a-Carba-PGI2 were transient. Our results suggest that the transient nature of the inhibition was neither caused by inactivation of these compounds, nor was it due to production in the cultures of an osteoclastic stimulator. CT, PGI2 and 6a-Carba-PGI2 all appear to operate by increasing the intracellular cyclic AMP level. We found no refractoriness to either CT, dibutyryl cyclic AMP or 8-bromo cyclic AMP, and neither PGI2 nor 6a-Carba-PGI2 affected the sensitivity of osteoclasts to CT or dibutyryl cyclic AMP. This implies that refractoriness of osteoclasts to PGI2 and 6a-Carba-PGI2 develops at some stage in the interaction between PG and cell proximal to cyclic AMP production. We also found that there was cross-tachyphylaxis between PGI2 and 6a-Carba-PGI2, and this suggests that these two compounds share a receptor site on osteoclasts.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002465:Cell Movement / Q000187:drug effects; D003513:Cycloheximide / Q000494:pharmacology; D011464:Epoprostenol / Q000494:pharmacology* / Q000031:analogs & derivatives; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007700:Kinetics; D010010:Osteoclasts / Q000187:drug effects / Q000502:physiology*; D011453:Prostaglandins / Q000494:pharmacology*; D051381:Rats; D013806:Theophylline / Q000494:pharmacology
D007042:Hypoxanthines; D007093:Imidazoles; D011453:Prostaglandins; D019271:Hypoxanthine; C026678:carboprostacyclin; C029899:imidazole; D003513:Cycloheximide; D013806:Theophylline; D011464:Epoprostenol; D015056:1-Methyl-3-isobutylxanthine