FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1593013521> ?p ?o ?g. }

• W1593013521 endingPage "15885" @default.
• W1593013521 startingPage "15875" @default.
• W1593013521 abstract "The mechanism of uptake of a series of amiloride derivatives by human neutrophils was investigated using [14C]amiloride and the 14C-labeled 5-(1-hexahydroazepinyl)-6-bromo analogue (BrMM) which is approximately 500-fold more potent than the parent compound at inhibiting Na+/H+ exchange. At an external concentration of 2 microM, the influx of BrMM at 37 degrees C was rapid, reaching a steady state by approximately 20 min. The rate of BrMM uptake (approximately 25 mumol/liter.min) was approximately 90-fold faster than for the same concentration of amiloride, a finding which correlates with differences in lipid partitioning of the two compounds. Uptake was unrelated to specific binding to Na+/H+ exchange transport sites: influx of either drug was nonsaturable whereas amiloride- and BrMM-mediated inhibition of Na+/H+ countertransport obeyed Michaelis-Menten kinetics with apparent Ki values of approximately 75 and approximately 0.2 microM. Entry occurred exclusively via the neutral (uncharged) forms (pK'a 8.40-8.55). Influx was markedly pH-dependent: it was enhanced by extracellular alkalinization and reduced by acidification. Influx was, however, insensitive to large changes in membrane voltage, thereby implying the protonated (charged) species to be impermeant. About 75% of the total intracellular pool of amiloride, but only approximately 25% of BrMM, is contained within the lysosomes, an expected consequence of the partitioning and subsequent trapping of a weak base within this strongly acidic subcellular compartment. With BrMM, there was a relative approximately 60-fold enrichment in the internal/external water concentration ratio of the drug; the value for amiloride was much less, approximately 4. This disparity is consistent with substantial binding of BrMM to internal constituents, presumably to proteins and/or nucleic acids. Thus, it is important to recognize that potentially large intracellular accumulations of potent analogues can occur that are not directly involved in inhibition of Na+/H+ exchange. These findings sound a cautionary note in the interpretation of results using these drugs in all cells, especially those of small size with high surface-to-volume ratios." @default.
• W1593013521 created "2016-06-24" @default.
• W1593013521 creator A5052420198 @default.
• W1593013521 creator A5089801903 @default.
• W1593013521 creator A5049967354 @default.
• W1593013521 date "1987-11-01" @default.
• W1593013521 modified "2023-09-30" @default.
• W1593013521 title "Intracellular accumulation of potent amiloride analogues by human neutrophils." @default.
• W1593013521 cites W1547972279 @default.
• W1593013521 cites W1558267681 @default.
• W1593013521 cites W1578086030 @default.
• W1593013521 cites W1645602382 @default.
• W1593013521 cites W1649730470 @default.
• W1593013521 cites W1913357042 @default.
• W1593013521 cites W1967385700 @default.
• W1593013521 cites W1975658051 @default.
• W1593013521 cites W1984808530 @default.
• W1593013521 cites W1996100314 @default.
• W1593013521 cites W2001166114 @default.
• W1593013521 cites W2001197606 @default.
• W1593013521 cites W2002089729 @default.
• W1593013521 cites W2012195659 @default.
• W1593013521 cites W2014839716 @default.
• W1593013521 cites W2015753314 @default.
• W1593013521 cites W2022641267 @default.
• W1593013521 cites W2048306533 @default.
• W1593013521 cites W2057661730 @default.
• W1593013521 cites W2077322809 @default.
• W1593013521 cites W2084725128 @default.
• W1593013521 cites W2087893811 @default.
• W1593013521 cites W2114800231 @default.
• W1593013521 cites W2120199157 @default.
• W1593013521 cites W2132364427 @default.
• W1593013521 cites W2140994830 @default.
• W1593013521 cites W2150922838 @default.
• W1593013521 cites W2318996479 @default.
• W1593013521 cites W2338885223 @default.
• W1593013521 cites W2406474239 @default.
• W1593013521 cites W2418118297 @default.
• W1593013521 cites W4238605098 @default.
• W1593013521 doi "https://doi.org/10.1016/s0021-9258(18)47670-3" @default.
• W1593013521 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/3680230" @default.
• W1593013521 hasPublicationYear "1987" @default.
• W1593013521 type Work @default.
• W1593013521 sameAs 1593013521 @default.
• W1593013521 citedByCount "18" @default.
• W1593013521 countsByYear W15930135212012 @default.
• W1593013521 countsByYear W15930135212023 @default.
• W1593013521 crossrefType "journal-article" @default.
• W1593013521 hasAuthorship W1593013521A5049967354 @default.
• W1593013521 hasAuthorship W1593013521A5052420198 @default.
• W1593013521 hasAuthorship W1593013521A5089801903 @default.
• W1593013521 hasBestOaLocation W15930135211 @default.
• W1593013521 hasConcept C178790620 @default.
• W1593013521 hasConcept C185592680 @default.
• W1593013521 hasConcept C2779608910 @default.
• W1593013521 hasConcept C537181965 @default.
• W1593013521 hasConcept C55493867 @default.
• W1593013521 hasConcept C79879829 @default.
• W1593013521 hasConcept C86803240 @default.
• W1593013521 hasConcept C95444343 @default.
• W1593013521 hasConceptScore W1593013521C178790620 @default.
• W1593013521 hasConceptScore W1593013521C185592680 @default.
• W1593013521 hasConceptScore W1593013521C2779608910 @default.
• W1593013521 hasConceptScore W1593013521C537181965 @default.
• W1593013521 hasConceptScore W1593013521C55493867 @default.
• W1593013521 hasConceptScore W1593013521C79879829 @default.
• W1593013521 hasConceptScore W1593013521C86803240 @default.
• W1593013521 hasConceptScore W1593013521C95444343 @default.
• W1593013521 hasIssue "33" @default.
• W1593013521 hasLocation W15930135211 @default.
• W1593013521 hasOpenAccess W1593013521 @default.
• W1593013521 hasPrimaryLocation W15930135211 @default.
• W1593013521 hasRelatedWork W1965267544 @default.
• W1593013521 hasRelatedWork W1986876542 @default.
• W1593013521 hasRelatedWork W1989710391 @default.
• W1593013521 hasRelatedWork W2026264997 @default.
• W1593013521 hasRelatedWork W2037737642 @default.
• W1593013521 hasRelatedWork W2072243940 @default.
• W1593013521 hasRelatedWork W2079692793 @default.
• W1593013521 hasRelatedWork W2616010456 @default.
• W1593013521 hasRelatedWork W300588050 @default.
• W1593013521 hasRelatedWork W97780958 @default.
• W1593013521 hasVolume "262" @default.
• W1593013521 isParatext "false" @default.
• W1593013521 isRetracted "false" @default.
• W1593013521 magId "1593013521" @default.
• W1593013521 workType "article" @default.