Sucralfate protection of gastric mucosa against alcohol-induced injury: a phosphoinositide mediated process

The mechanism of protection by sucralfate against gastric mucosal injury induced by ethanol was investigated. The experiments in vivo were conducted with groups of rats with and without indomethacin pretreatment, and the animals received sucralfate followed by ethanol. In the in vitro experiments, gastric mucosa was cultured in the presence of sucralfate, ethanol, or both. The in vivo experiments revealed that ethanol caused extensive gastric hemorrhagic lesions which were significantly reduced following sucralfate pretreatment and that this effect of sucralfate was not prevented by indomethacin. The data with gastric mucosal culture demonstrated that ethanol caused a 24% decrease in mucin synthesis, while mucin synthesis in the presence of sucralfate increased by 32%. This increase was accompanied by the enhanced metabolism of mucosal phosphoinositides, as reflected by a 22% decrease in PI, 1,2-fold increase in IP1 and 3.4-fold increase in IP3. In contrast, ethanol, caused 1.5-fold increase in IP1 and PIP2, and 35% decrease in PIP, 47% decrease in IP2 and 38% decrease in IP3. However, when the mucosal culture was carried out in the presence of both sucralfate and ethanol, the detrimental changes evoked by ethanol in mucin synthesis were prevented. The results suggest that the mucosal protective action of sucralfate involves the metabolism of phosphoinositide-derived messenger molecules.     

Phylogeny of Greya (Lepidoptera: Prodoxidae), based on nucleotide sequence variation in mitochondrial cytochrome oxidase I and II: congruence with morphological data

The phylogeny of Greya Busck (Lepidoptera: Prodoxidae) was inferred from nucleotide sequence variation across a 765-bp region in the cytochrome oxidase I and II genes of the mitochondrial genome. Most parsimonious relationships of 25 haplotypes from 16 Greya species and two outgroup genera (Tetragma and Prodoxus) showed substantial congruence with the species relationships indicated by morphological variation. Differences between mitochondrial and morphological trees were found primarily in the positions of two species, G. variabilis and G. pectinifera, and in the branching order of the three major species groups in the genus. Conflicts between the data sets were examined by comparing levels of homoplasy in characters supporting alternative hypotheses. The phylogeny of Greya species suggests that host-plant association at the family level and larval feeding mode are conservative characters. Transition/transversion ratios estimated by reconstruction of nucleotide substitutions on the phylogeny had a range of 2.0-9.3, when different subsets of the phylogeny were used. The decline of this ratio with the increase in maximum sequence divergence among taxa indicates that transitions are masked by transversions along deeper internodes or long branches of the phylogeny. Among transitions, substitutions of A-->G and T-->C outnumbered their reciprocal substitutions by 2-6 times, presumably because of the approximately 4:1 (77%) A+T-bias in nucleotide base composition. Of all transversions, 73%-80% were A<-->T substitutions, 85% of which occurred at third positions of codons; these estimates did not decrease with an increase in maximum sequence divergence of taxa included in the analysis. The high frequency of A<-->T substitutions is either a reflection or an explanation of the 92% A+T bias at third codon positions.      

Regulation of Cyclic AMP Levels by Calcium in Bovine Adrenal Medullary Cells

Both nicotine and histamine have been reported to increase cyclic AMP levels in chromaffin cells by Ca(2+)-dependent mechanisms. The present study investigated whether Ca2+ was an adequate and sufficient signal for increasing cyclic AMP in cultured bovine adrenal medullary cells. Depolarization with 50 mM K+ caused a two- to three-fold increase in cellular cyclic AMP levels over 5 min, with no change in extracellular cyclic AMP. This response was abolished by omission of extracellular Ca2+ and by 100 microM methoxyverapamil, and was unaffected by 1 microM tetrodotoxin and by 1 mM isobutylmethylxanthine. Veratridine (40 microM) also increased cellular cyclic AMP levels by two- to fourfold. This response was abolished by either methoxyverapamil or tetrodotoxin. The Ca2+ ionophore A23187 (10-50 microM) had little or no effect on cellular cyclic AMP levels. When the concentration of K+ used to depolarize the cells was reduced to 12-15 mM, the catecholamine release was similar to that induced by 50 microM A23187, and the cyclic AMP response was almost abolished. The results suggest that Ca2+ entry into chromaffin cells is a sufficient stimulus for increasing cellular cyclic AMP production. The possible involvement of a Ca2+/calmodulin-dependent isozyme of adenylate cyclase is discussed.