Dynamics simulation, energetics calculation and experimental analysis of the intermolecular interaction between human neonatal ABL SH3 domain and its -substituted peptoid ligands.

Non-receptor tyrosine kinase of neonatal ABL (nABL) is distributed in the nucleus and cytoplasm of proliferating cells in embryo and neonate, and has been implicated in the pathogenesis of neonatal leukemia and other hematological diseases. The kinase contains a regulatory Src homology 3 (SH3) domain that can specifically recognize proline-rich peptide segments on its partner protein surface. In this study, we systematically investigated the -substitution effect on the binding of an empirically designed proline-rich peptide p9 to nABL SH3 domain by integrating dynamics simulations, energetics calculations and fluorescence affinity assays.

D(1) dopamine receptor stimulation increases GluR1 phosphorylation in postnatal nucleus accumbens cultures.

Postsynaptic interactions between dopamine and glutamate receptors in the nucleus accumbens are critical for acute responses to drugs of abuse and for neuroadaptations resulting from their chronic administration. We tested the hypothesis that D(1) dopamine receptor stimulation increases phosphorylation of the AMPA receptor subunit GluR1 at the protein kinase A phosphorylation site (Ser845). Nucleus accumbens cell cultures were prepared from postnatal day 1 rats.

Repeated administration of amphetamine or cocaine does not alter AMPA receptor subunit expression in the rat midbrain.

We previously reported that ventral tegmental area (VTA) dopamine neurons are supersensitive to AMPA when recorded three days after discontinuing repeated amphetamine or cocaine administration. By increasing dopamine cell activity, this may contribute to the induction of behavioral sensitization. The goal of this study was to determine if increased sensitivity to AMPA reflects increased AMPA receptor expression in the midbrain.