Growth-promoting activity of desmopressin in murine leukemia cells treated in vitro.
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 less than 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 less than 0.001). This phenomenon was associated with significant elevations of 1,2[3H] diacylglycerol after incubation with dDAVP for 9 min (P less than 0.01) and of total [3H]diacylglycerols after incubation for both 3 min (P less than 0.05) and 9 min (P less than 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.
Beenken
S W
SW
Manitoba Institute of Cell Biology, University of Manitoba, Winnipeg, Canada.
Batra
J K
JK
Gerrard
J M
JM
Goldenberg
G J
GJ
D000818:Animals; D002999:Clone Cells; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology*; D004075:Diglycerides / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism; D007940:Leukemia L5178 / Q000378:metabolism / Q000473:pathology*; D007941:Leukemia P388 / Q000473:pathology; D007942:Leukemia, Experimental / Q000473:pathology*; D008558:Melphalan / Q000493:pharmacokinetics; D051379:Mice; D014667:Vasopressins / Q000494:pharmacology
C011439:1,2-diacylglycerol; D004075:Diglycerides; D007295:Inositol Phosphates; D014667:Vasopressins; D003894:Deamino Arginine Vasopressin; D008558:Melphalan