EVIDENCE FOR CAMP-INDEPENDENT INHIBITION OF S-PHASE DNA-SYNTHESIS BY PROSTAGLANDINS

  • 1 January 1983
    • journal article
    • research article
    • Vol. 258  (1) , 491-496
Abstract
Two prostaglandins [PG], PGE1 and PGB1, block S-phase DNA synthesis in synchronous cultured baby hamster kidney (BHK) cells. The PG inhibition of DNA synthesis does not appear to require elevated levels of cAMP. In BHK-21 cells that have been desensitized to PG stimulation of adenylate cyclase, and therefore have control levels of cAMP, PGE1 retains its inhibitory effect on the incorporation of 3H-thymidine into DNA. When BHK cells are exposed to PGB1 (a PG that does not elicit a cAMP response), DNA synthesis is also blocked. In nonsynchronous cells exposed for 1 h to PGE and then incubated for 1 h with PGE removed, a rebound of DNA synthesis occurs, therefore providing evidence that a transient rise of cAMP in itself is not capable of causing a cascade of reactions that block the synthesis of DNA. In addition, the concentration of PGE required for inhibition of DNA synthesis is significantly less than that required for cAMP generation. Addition of 1 .times. 10-8 M PGE to BHK cells significantly inhibits DNA synthesis within 30 min, with half-maximal inhibition at 3 .times. 10-7 M PGE. cAMP levels for controls were 4.9 .+-. 0.2 and 4.6 .+-. 0.1 for 1 .times. 10-6 M PGE1. Apparently, PG can act independently of cAMP at physiological concentrations, and therefore it is possible that PG have a physiological role in the control of cell growth during S-phase.