The effect of dibutyryl cyclic AMP and PGE2 on lysosomal enzyme release and lactate production in relation to bone resorption in vitro.

The effect of dibutyryl cyclic AMP (dbc AMP) and PGE2 on the content and release of lysosomal and non-lysosomal enzymes was studied in a bone organ culture system using half calvaria from 6-7 day-old mice. In parallel the effect of dbc AMP and PGE2 on the release of calcium (Ca2+) and inorganic phosphate (Pi), glucose consumption and lactate production was also followed. DbcAMP (2.5 X 10(-4) M) decreased the release of beta-glucuronidase, beta-N-acetyl-glucosaminidase, acid phosphatase, Ca2+ and Pi during the first day of culture. During the 3rd and 4th day of dbcAMP increased all these parameters. In contrast no changes in the release of lactate dehydrogenase (LDH) and alanine aminotransferase (ALAT) were seen. Glucose consumption and lactate production was not stimulated by dbcAMP until the 3rd and 4th day. On the other hand, PGE2 (10(-7) M) stimulated the release of beta-glucuronidase, beta-N-acetylglucosaminidase, Ca2+ and Pi as well as glucose consumption and lactate production already after 24 h and this stimulation was maintained throughout the culture period. No effect by PGE2 on the release of LDH and ALAT was registered. The activities of LDH in the bone explants after 96 h of culture were significantly augmented by both dbcAMP and PGE2. It is concluded that bone resorption stimulated by dbcAMP and PGE2, is associated lysosomal enzyme release and lactate production.