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Cyclic GMP is another attractive candidate for a second messenger. This nucleotide rises in lymphocytes stimulated with phytohemagglutinin or concanavalin A and in resting mouse fibroblasts stimulated by serum(85,86).These findings have suggested that an increase in cyclic GMP levels may serve as a mitogenic signal.Moreover,EP produces a marked increase in the cyclic GMP concentration in rabbit marrow and fetal liver cells (87,88).However,this increase does not occur until at least 1.5 hr after addition of the hormone(88).since ep is known to increase RNA synthesis in fetal liver and marrow cells within minutes,cyclic GMP does not appear to represent a messenger in that process,but may be involved in a later aspect of the hormone is effect.
a third candidate for a sencond messenger has recently been described by Chang and Goldwasser (89).they extracted a cytoplasmic fraction from EP-treated rat marrow cells that stimulated RNA synthesis in marrow cell nuclei. A similar cytoplasmic fraction from EP-treated kidney and lung cells, and EP itself,were inactive.the production of an active fraction appeared to depend on the presence of marrow cell cytoplasmic membrane or intact cells,since the in-cubation of ep with normal marrow cell cytosol did not lead to active material.the factor appeared promptly after addition of EP and peaked within =1hr.although inactivation by trypsin suggested that it had a peptide structure,inhibition of protein synthesis did not block its appearance.these experiments suggest that ep has its primary effect on the cytoplasmic membrane of marrow cell to produce an active cytoplasmic protein intermediate that interacts with the nucleus to stimulate synthesis of a variety of RNAs.

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