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Effect of prostaglandin i 2 and 6a carba prostaglandin i 2 on the motility of isolated osteoclasts


, : Effect of prostaglandin i 2 and 6a carba prostaglandin i 2 on the motility of isolated osteoclasts. Prostaglandins 25(5): 603-614

Calcitonin (CT), a hormone which inhibits osteoclastic bone resorption, completely abolishes the normally intense cytoplasmic movement of isolated [rat] osteoclasts. Prostaglandin (PG)I2 causes an identical change in behavior. Investigations into the mode of action of PGI2 and a stable analog, 6a-carba-PGI2 were examined. Unlike CT which causes prolonged immotility in osteoclasts, the effect of PGI2 and 6a-carba-PGI2 was transient. Apparently 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 cAMP level. No refractoriness to either CT, dibutyryl cAMP or 8-bromo cAMP was found, and neither PGI2 nor 6a-carba-PGI2 affected the sensitivity of osteoclasts to CT or dibutyryl cAMP. 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 cAMP production. There was cross-tachyphylaxis between PGI2 and 6a-carba-PGI2, and this suggests that these 2 compounds share a receptor site on osteoclasts.

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