In synaptosomes, MDMA decreased 5-HT uptake by about 40%. This decrease was prevented by MEM and by MLA but enhanced by PNU 282987. A similar pattern was observed when we measured the dopamine transport inhibited by METH. The inhibition of both transporters by amphetamine derivatives seems to
be regulated by the calcium incorporation after APR-246 activation of alpha-7 nAChR. MDMA competitively displaces [H-3]MLA from rat brain membranes. MEM and METH also displace [H-3]MLA with non-competitive displacement profiles that fit a two-site model. We conclude that MEM prevents MDMA and METH effects in rodents. MEM may offer neuroprotection against neurotoxicity induced by MDMA and METH by preventing the deleterious effects of these amphetamine derivatives on their respective transporters. (c) 2008 Elsevier Ltd. All rights reserved.”
“Autographa californica multiple nucleopolyhedrovirus (AcMNPV) BV/ODV-c42 (orf101; c42), which encodes a 41.5-kDa viral nucleocapsid protein with a putative nuclear localization signal (NLS) motif at the C terminus, is a highly conserved gene among members of the Baculoviridae
family. C42 is demonstrated to be essential for AcMNPV propagation and can bind to nucleocapsid mTOR inhibitor protein P78/83, a viral activator for the actin-related protein 2/3 (ARP2/3) complex to initiate nuclear actin polymerization, which is essential for viral nucleocapsid morphogenesis during AcMNPV infection. Here, we report the identification of
a novel pathway through which c42 functions in nucleocapsid assembly. Cotransfection of Sf9 cells with c42 and p78/83 plasmids demonstrated that C42 was capable of recruiting P78/83 to the nuclei of uninfected cells and that the NLS motif of C42 was essential for this process. To validate this nuclear relocation mode in bacmid-transfected cells, a c42-disrupted bacmid (vAc(c42ko-gfp)) and rescued bacmids with wild-type c42 (vAcc42(res-gfp)) or with NLS coding sequencemutated c42 (vAcc42(nls-gfp)) were prepared. By immuno-staining, P78/83 was found to be localized in the cytoplasm of either vAc(c421ko-gfp) – or vAc(c42nls-gfp)-transfected cells, whereas P78/83 was relocated to the nuclei of VAC(c42res-gfP)-transfected why cells. Furthermore, F-actin-specific staining confirmed that there was no actin polymerization activity in the nuclei of either vAc(c42ko-gfp) – or vAv(c42nls-gfP)-transfected cells, which might be attributed to the absence of nuclear P78/83, an activator of the ARP2/3 complex to initiate nuclear actin polymerization. We therefore hypothesize a mode of action where C42 binds to P78/83 in the cytoplasm to form a protein complex and cotransports to the nucleus under the direction of the NLS motif in C42 during AcMNPV infection.”
“Morphine treatment can paradoxically increase nociception (i.e. hyperalgesia).