RAPID INHIBITION OF INTERCELLULAR COMMUNICATION BETWEEN BALB/C 3T3 CELLS BY DIACYLGLYCEROL, A POSSIBLE ENDOGENOUS FUNCTIONAL ANALOG OF PHORBOL ESTERS

  • 1 January 1985
    • journal article
    • research article
    • Vol. 45  (8) , 3706-3710
Abstract
Intercellular communication between cultured cells is reversibly inhibited by phorbol ester tumor promoters, which activate protein kinase C directly, replacing the role of diacylglycerol. In order to see whether a presumed endogenous functional analog, a diacylglycerol, could inhibit intercellular communication in the same way as phorbol esters, the effects were compared of 1-oleoyl-2-acetyl-glycerol (OAG) and 12-O-tetradecanoylphorbol-13-acetate (TPA) on intercellular communication between BALB/c 3T3 [mouse] cells, using a fluorescent dye transfer method. When cells were treated with OAG, dose-dependent inhibition of dye transfer between cells was observed, which was almost complete with OAG at 50 .mu.g/ml. The effect was rapid, a maximal effect occurring within 30 min after addition. The inhibitory effect of both compounds was maintained for at least for 4 h when the cells were in the growing phase; thereafter, the capacity to transfer dye recovered gradually and then returned to the control level after 8 or 12 h of treatment with OAG or TPA, respectively. Further additions of OAG or TPA had no effect. When OAG was added to cultures during a refractory period produced by TPA, the culture was also refractory to OAG; however, TPA could induce at least 60% inhibition of dye transfer in cultures that had been made refractory to OAG. However, when cultures that had been made refractory to TPA were washed and then OAG was added, it induced extensive inhibition of dye transfer at any time after removal of TPA, whereas addition of TPA to the culture caused no significant reinhibition by 6 h and was detectable only 9 h after removal of TPA. Apparently, OAG can inhibit dye transfer in a similar manner to TPA, suggesting that activation of protein kinase C may be a mechanism by which phorbol esters inhibit intercellular communication. There is apparently some difference between the mechanisms by which OAG and TPA inhibit intercellular communication.

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