Marylmd 2 7224
In Swiss 3T3. murine fibroblasts, interleukin 1 (IL-1) and bradykinin stimulate prostdglandin E, (PGE,) synthesis. However, in the present study, we found that neither agonisi stimulated PGE, synthesis in BALBic 3T3 murine fibroblasts, this in spite of expression of similar numbers of receptors tor rach agonist compared to Swiss 3T3 cells. When BALBic 3T3 cells were preincubated with CAMP analogs, both IL-1 and bradykinin stimulated PGE, synthesis to levels similar to those observed in Swiss 3T3 cells. Similarly, when the cells were preincubated with forskolin, which activates the catalytic subunit of adenylate cyclase directly, or NECA, which stimulates cellular cAMP accumulation by activating adenosine receptors, IL-l and bradykinin stimulated PGE, synthesis. Rp-CAMPS, an inhibitor of CAMP-dependent protein kinase, blocked the ability of CAMP or NECA to render cells responsive to IL-1 and bradykinin. In basal BALBIc 3T3 cells, bradykinin and IL-I stimulated arachidonate release in the absence of CAMP, but littlc conversion of released arxhidonate to PGE, occurred. CAMP, forskolin, and NECA all increased cyclooxygenase activity in the cells. SV-T2 is a clonal line originating from BALBlc 3T3 transformed with SV-40. In these cells, I L -l and bradykinin stimulated PGE, synthesis despite basal intracellular CAMP concentrations similar to BALBic, and CAMP only modestly potentiated the response. In summary, cyclooxygenase expression appears to be regulated by CAMP in BALKic 3T3 cells, and SV-40 transformation results in increased cyclooxygenase expression, apparently independent of CAMP.