Accumulation of glutamate by osmotically stressed Escherichia coli is dependent on pH.

In the present study, we measured the accumulation of glutamate after hyperosmotic shock in Escherichia coli growing in synthetic medium. The accumulation was high in the medium containing sucrose at a pH above 8 and decreased with decreases in the medium pH. The same results were obtained when the hyperosmotic shock was carried out with sodium chloride. The internal level of potassium ions in cells growing at a high pH was higher than that in cells growing in a neutral medium. A mutant deficient in transport systems for potassium ions accumulated glutamate upon hyperosmotic stress at a high pH without a significant increase in the internal level of potassium ions. When the medium osmolarity was moderate at a pH below 8, E. coli accumulated gamma-aminobutyrate and the accumulation of glutamate was low. These data suggest that E. coli uses different osmolytes for hyperosmotic adaptation at different environmental pHs.

Synthesis and antiinflammatory and analgesic properties of 2-amino-1H-benzimidazole and 1,2-dihydro-2-iminocycloheptimidazole derivatives.

2-Amino-1H-benzimidazoles (3) and 1,2-dihydro-2-iminocycloheptimidazoles (4) were synthesized and evaluated for antiinflammatory and analgesic activities. The compounds in the series 3 were synthesized via phenylthioureas (6) or 2-chloro-1H-benzimidazole (12). Most of 4 were synthesized by two methods. One was the reaction of carbodiimides (14) with 2-amino-2,4,6-cycloheptatrien-1-one (method A). The other was the reaction of guanidines (15) with 2-chloro-2,4,6-cycloheptatrien-1-one (method B). Some of the compounds 3 and 4 exhibited potent antiinflammatory and analgesic activities when compared to timegadine (1) or tiaramide hydrochloride (HCl) (17). It was of interest that 1-(2-benzothiazolyl)-2-cyclohexylimino-1,2-dihydrocycloheptimid azole (4e) showed superior analgesic activity to timegadine or tiaramide HCl (ED50 = 1.7 mg/kg p.o. in the acetic acid-induced writhing test, ED30 = 14.0 mg/kg p.o. in Randall-Selitto method) in spite of no effect on prostaglandin E2 synthesis.