The effect of dibutyryl cyclic AMP and PGE2on lysosomal enzyme release and lactate production in relation to bone resorption in vitro

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Abstract
The effect of dibutyryl cAMP (dbcAMP) and PG[prostaglandin]E2 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 dbcAMP and PGE2 on the release of calcium (Ca2+) and inorganic phosphate (Pi), glucose consumption and lactate production was also followed. DbcAMP (2.5 .times. 10-4 M) decreased the release of .beta.-glucuronidase, .beta.-N-acetyl-glucosaminidase, acid phosphatase, Ca2+ and Pi during the 1st day of culture. During the 3rd and 4th days dbcAMP increased all these parameters. No changes in the release of lactate dehydrogenase (LDH) and alanine aminotransferase (ALAT) were seen. Glucose consumption and lactate production were not stimulated by dbcAMP until the 3rd and 4th days. PGE2 (10-7 M) stimulated the release of .beta.-glucuronidase, .beta.-N-acetylglucosaminidase, Ca2+, Pi, 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. Bone resorption stimulated by dbcAMP and PGE2 apparently is associated with increased lysosomal enzyme release and lactate production.