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Growth-promoting Activity of Desmopressin in Murine Leukemia Cells Treated in Vitro¹

The Manitoba Institute of Cell Biology [S. B., J. K. B., J. M. G., G. J. G.], Department of Medicine [G. J. G.], and the Department of Pediatrics [J. M. G.], University of Manitoba, Winnipeg, Manitoba, Canada R3E 0V9

The synthetic vasopressin analogue, desmopressin (dDAVP), has been shown to influence membrane transport of melphalan in murine L5178Y lymphoblasts. Accordingly, the effect of dDAVP on the cytocidal activity of melphalan in L5178Y cells was evaluated. dDAVP did not affect the cytocidal activity of melphalan in these cells, but significantly affected the cloning efficiency of stationary phase or slowly dividing L5178Y cells over a range of concentrations. In particular, stationary phase cells showed an increase in cloning efficiency from 4.3 ± 0.5% in control cells to 7.0 ± 0.3% in cells treated with 25 nM dDAVP (P < 0.001), whereas cells doubling every 26 h showed an increase from 10.8 ± 1.2% in control cells to 21.0 ± 2.0% in cells treated with 150 nM dDAVP (P < 0.001). This phenomenon was associated with significant elevations of 1,2[³H] diacylglycerol after incubation with dDAVP for 9 min (P < 0.01) and total [³H]diacylglycerols after incubation for both 3 min (P < 0.05) and 9 min (P < 0.02). Within 10 s of treatment with 100 nM dDAVP, there was a marked decrease in the levels of inositol 1,4,5-trisphosphate and inositol 1-phosphate, but subsequently no change was observed for up to 9 min after treatment. We postulate that the increase of diacylglycerol content produced by dDAVP might be primarily from a phosphatidylcholine source and that the growth-promoting activity of desmopressin may be a consequence of activation of protein kinase C.

¹ This work was supported by a grant from the National Cancer Institute of Canada (to J. M. G. and G. J. G.).

² Terry Fox Fellow of the National Cancer Institute of Canada.

³ To whom requests for reprints should be addressed, at Manitoba Institute of Cell Biology, 100 Olivia St., Winnipeg, Manitoba, Canada R3E 0V9.

Received 5/12/88. Revised 8/11/88. Accepted 9/ 2/88.