We previously reported that a methanolic extract of Coptis japonica, which is a well-known traditional oriental medicine, inhibits morphine-induced conditioned place preference (CPP) in mice. Berberine is a major component of Coptis japonica extract, and it has been established that the adverse effects of morphine on the brain involve dopamine (DA) receptors. However, to our knowledge, no study has investigated the inhibitory effects of berberine on morphine-induced locomotor sensitization and analgesic tolerance in mice. Here, we investigated the effects of berberine on morphine-induced locomotor sensitization and on the development of analgesic tolerance. Furthermore, we examined the effects of berberine treatment on N-methyl-d-aspartate (NMDA) receptor channel activity expressed in Xenopus laevis oocytes. Berberine was found to completely block both morphine-induced locomotor sensitization and analgesic tolerance, and reduce D1 and NMDA receptor bindings in the cortex. Moreover, berberine markedly inhibited NMDA current in Xenopus laevis oocytes expressing NMDA receptor subunits. Our results suggest that the inhibitory effects of berberine on morphine-induced locomotor sensitization and analgesic tolerance are closely related to the modulation of D1 and NMDA receptors, and that berberine should be viewed as a potential novel means of attenuating morphine-induced sensitization and analgesic tolerance.

Epidermolytic palmoplantar keratoderma (EPPK) is an autosomal dominant disorder, which presents as palmoplantar skin blistering, due to cytolysis in the suprabasal layers. A mutation of the keratin genes of a Korean patient with EPPK was investigated through DNA sequence analyses of the keratin 1 (KRT1) and keratin 9 (KRT9) genes. No remarkable mutations were found in the KRT9 gene, however, two novel base substitutions were found in the KRT1 gene. One, G --> T transversion leading to an amino acid substitution Gly (GTG) to Cys (GTT) (G137C) in the head VI domain, and another, T --> A transversion, Phe (TTC) to Ile (ATC) (F1941) in the rod 1A domain. In order to verify the polymorphism of these mutations, allele specific-PCR (AS-PCR) was carried out with mutation-specific primers for each mutation. Mutant products from the G137C and F1941 were only produced from the EPPK patients at annealing temperatures of 65 and 64degreesC, respectively. These results show that two mutations, in the head and rod 1A region of the KRT1 gene, are specific to this Korean pedigree, and might be closely related with EPPK.

Glial cells play many roles in the development and function of complex nervous systems. These roles include structural support, wrapping and insulating neurons, regulating neurons with cytokines and growth factors, controling the proper ionic environment, modulating synaptic activity and regulating synapse numbers. So understanding of how cellular specification, differentiation and interactions of glial cells are regulated during nervous system development is a fundamental question in developmental neurobiology. In this study, the roles of spitz/Egfr signaling, which has been required for the proper development of the ventral neuroectoderm, was investigated in patterning of several kinds of glial cells. Several enhancer trap lines were used as each glial cell marker gene. The loss-of-function mutation of spi and Egfr reduced expression of A and B subperineural glia, longitudinal glia, exit glia and peripheral glia. The spitz/Egfr signaling has greater effect on CNS glia than on PNS glia, indicating that spitz/Egfr signaling is involved in patterning of glia with a graded fassion along D/V axis.

Saccharomyces cerevisiae Ste5 is a scaffold protein that recruits many pheromone signaling molecules to sequester the pheromone pathway from other homologous mitogen-activated protein kinase pathways. G1 cell cycle arrest and mating are two different physiological consequences of pheromone signal transduction and Ste5 is required for both processes. However, the roles of Ste5 in G1 arrest and mating are not fully understood. To understand the roles of Ste5 better, we isolated 150 G1 cell cycle arrest defective STE5 mutants by chemical mutagenesis of the gene. Here, we found that two G1 cell cycle arrest defective STE5 mutants (ste5M(D248V) and ste5(delta-776)) retained mating capacity. When overproduced in a wild-type strain, several ste5 mutants also showed different dominant phenotypes for G1 arrest and mating. Isolation and characterization of the mutants suggested separable roles of Ste5 in G1 arrest and mating of S. cerevisiae. In addition, the roles of Asp-248 and Tyr-421, which are important for pheromone signal transduction were further characterized by site-directed mutagenesis studies.