The effect of prostaglandin I 2 and 6a-Carba-PGI 2 on the motility of isolated osteoclasts

Abstract

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)I 2 causes an identical change in behaviour. In this paper we extend our investigations into the mode of action of PGI 2 and a stable analogue, 6a-Carba-PGI 2. We found that, unlike CT which causes prolonged immotility in osteoclasts, the effect of PGI 2 and 6a-Carba-PGI 2 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, PGI 2 and 6a-Carba-PGI 2 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 PGI 2 nor 6a-Carba-PGI 2 affected the sensitivity of osteoclasts to CT or dibutyryl cyclic AMP. This implies that refractoriness of osteoclasts to PGI 2 and 6a-Carba-PGI 2 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 PGI 2 and 6a-Carba-PGI 2, and this suggests that these two compounds share a receptor site on osteoclasts.