Association in normal human fibroblasts of elevated levels of adenosine 3‘:5‘-monophosphate with a selective decrease in collagen production.

To evaluate the hypothesis that extracellular mediators may affect collagen production by mesenchymal cells via a cyclic AMP coordinated mechanism, normal human fibroblasts were exposed to a variety of agents (prostaglandin E1, isoproterenol, cholera toxin) which independently elevated intracellular cyclic AMP during a 6-h incubation. Concomitantly, each agent caused an average 47% reduction in the percentage of total protein synthesis represented by collagen, yet little change in other major extracellular proteins. Since no active collagenase was found in these cultures, these findings suggest cyclic AMP levels may modulate the differentiated state of normal fibroblasts with respect to collagen production.