D2s dopamine receptor mediates phospholipase D and antiproliferation.
The D2 dopamine receptor, short form (D2s) has been shown to stimulate phospholipase D (PLD) activity independent of activation of phospholipase C (PLC) activity in GH4 derived cells stably transfected with the D2s receptor [Mol. Pharm. 58 (2000) 455]. Agonist activation of D2s has been shown to mediate the inhibition of growth in the same cell line [J. Biol. Chem. 276 (1992) 24169; Endocrinology 134 (1994) 783]. In the present study, D2s-HEK 293 cells were generated using Epstein-Barr virus (EBV) based vectors. The stimulation of PLD by D2s can be augmented by the transfection of Rho A, but not Cdc 42 or Rac and nullified by transfection of N19 Rho A, a dominant negative form of Rho A. Addition of ethanol, at 0.5% reduced the ability of dopamine agonists to inhibit growth in D2s-HEK 293 cells, suggesting that PLD is involved in the antiproliferative effects of D2s signaling. In addition, the expression of N19 Rho A ablated the ability of the D2s to inhibit [3H]thymidine incorporation, while the expression of N19 Cdc 42 or N17 Rac had no effect. These results suggest that the D2s stimulation of PLD is Rho A dependent and lies along the signaling pathway which leads to the antiproliferative effects of D2s receptor activation.
Senogles
Susan E
SE
Department of Molecular Sciences, College of Medicine, The University of Tennessee Health Science Center, 858 Madison Ave. Suite G01, Memphis, TN 38163, USA. ssenogles@utmem.edu
D000818:Animals; D002455:Cell Division; D002460:Cell Line; D000431:Ethanol / Q000494:pharmacology; D005822:Genetic Vectors; D010739:Phospholipase D / Q000378:metabolism*; D010957:Plasmids; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000378:metabolism*; D015398:Signal Transduction; D013936:Thymidine / Q000493:pharmacokinetics; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
D017448:Receptors, Dopamine D2; C113776:dopamine D2L receptor; D000431:Ethanol; D010739:Phospholipase D; D020764:cdc42 GTP-Binding Protein; D020744:rac GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein; D013936:Thymidine