N6,O2'-dibutyryl adenosine 3', 5'-monophosphate-stimulated release of proteoglycans from cultured immature rabbit ear cartilage.

The stimulatory effects of N6, O2'-dibutyrl adenosine 3',5'-monphosphate on proteoglycan released from immature rabbit ear cartilage were studied in viltro. Cartilage incubayed in medium containing dibutyryl cyclic AMP resulted in a significant increase of proteoglycans released in concentrations above 0.5 mM. Theophylline (1 mM) which did not significantly stimulate proteoglycans released alone, was found to potentiate the action of this nucleotide. ATP, 5'-AMP and butyric acid in the presence of theophylline, did not stimulate proteolgycans released. The addition of protein or RNA synthesis inhibitors depressed proteoglycans released by dibutyryl cyclic AMP and theophylline. Gel chromatogrphic and chemical investigation of the proteoglycans released into the culture media in the presence of dibutylic cyclic AMP indicated a reduction in the proportion of protein associated with these complexes. This result, together with enzyme inhbitor studies, leads us to speculate that the observed action of dibutyryl cyclic AMP on rabbit ear cartilages may be mediated by the neutral proteases.