Effect of Multiplication Stimulating Activity (MSA) on intracellular cAMP levels and adenylate cyclase activity in chick embryo fibroblasts

Abstract

The addition of the somatomedin-like growth factor Multiplication Stimulatory Activity (MSA) to intact chick embryo fibroblasts (CEF) in culture does not decrease the basal intracellular pool of cAMP. As a more sensitive means of determining a possible effect of MSA on cAMP metabolism we have assessed the ability of MSA to alter the accumulation of intracellular cAMP in response to added prostaglandin E 1 (PGE 1) to intact CEF. MSA exhibits a concentration-dependent inhibition of PGE 1-stimulated accumulation of cAMP in CEF, with maximal inhibition observed at 100–400 ng/ml MSA. The MSA inhibitory effect is rapid, occurring within minutes of MSA addition, and the extent of inhibition is not altered with increasing PGE 1 concentration. MSA is also effective in inhibiting both PGE 1- and fluoride-stimulated activities of CEF adenylate cyclase of crude membrane preparations. In the concentration range of 100–400 ng/ml, MSA causes a 20–40% inhibition of cyclase activity. It should be emphasized that it has not been shown that these MSA effects on cAMP metabolism are relevant to the mechanism for growth promotion by this factor.