Biological activities of avicatonin (synthetic (Asu1,7) chicken calcitonin) were investigated in vivo and in vitro. Avicatonin at a dose of 5 U/kg body wt. in mice rapidly decreased serum Ca level, as well as elcatonin did. The hypocalcemic effect lasted for at least 4 hr. In organ culture of mouse calvariae prelabeled with 45CaCl2, basal Ca release into medium was at low level and was not modulated by treatment with avicatonin. The avicatonin, however, strongly suppressed the stimulated Ca release by bone resorption activators such as 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), parathyroid hormone and prostaglandin E2. To elucidate the mechanism of the inhibitory effect of avicatonin on bone resorption, we examined its effect on the generation of multinucleated cells, which indicate the characteristics as osteoclasts, in bone marrow cell culture. The multinucleated cells with 10 nuclei or more induced by 1,25(OH)2D3 showed high motility and contained tartrate-resistant acid phosphatase, a marker enzyme of osteoclasts. Simultaneous addition of avicatonin with 1,25(OH)2D3 decreased the number of multinucleated cells dose-dependency. Moreover, the avicatonin ceased the motility of the multinucleated cells and strikingly changed their shape within a few minutes after its addition. These results indicate that the potent hypocalcemic activity of avicatonin may be due to the inhibition of both the generation and function of osteoclasts.
|Original language||English (US)|
|Number of pages||8|
|Journal||Japanese Pharmacology and Therapeutics|
|Issue number||SUPPL. 13|
|State||Published - Jan 1 1994|
ASJC Scopus subject areas
- Pharmacology (medical)