Journal article
Characterization of the effect of two 4-methyl piperidine derivatives of hemicholinium-3, A-4 and A-5, on choline transport
The Journal of pharmacology and experimental therapeutics, Vol.255(1), pp.357-363
10/1990
DOI: 10.1016/S0022-3565(25)12783-3
PMID: 2213567
Abstract
A-4 and A-5 are tertiary and N-methyl quaternary 4-methylpiperidine analogs of hemicholinium-3 (HC-3). Previous work in this laboratory has shown A-4 and A-5 to be inhibitors of the sodium-dependent, high affinity choline uptake system (SDHACU). Their effects on choline transport were characterized further using neuroblastoma 41A3 cells. These cells rapidly take up choline through two separate mechanisms: a SDHACU system and a sodium-independent, low affinity uptake system (SILACU). A-4, A-5 and HC-3 decreased 5 microM choline transport in a dose-dependent fashion. The compounds were unable to decrease choline transport at 250 microM choline suggesting that they are inactive with respect to SILACU. All three compounds significantly increased the Km but not the Vmax for the SDHACU system, suggesting a competitive mechanism of inhibition. Ki values ranged from 18 to 25 microM for A-4, 20 to 26 microM for A-5 and 68 to 75 microM for HC-3. Dose-response curves for inhibition of choline transport by A-5 and HC-3 were not changed by a 24-hr pre-exposure of the cells to each inhibitor. However, after a 24-hr pre-exposure to A-4, a significantly different dose-response curve was obtained compared to the dose-response curve for A-4 in untreated cells. After a 24-hr pre-exposure, a 4-hr recovery period was sufficient to remove the effect of each compound. These data suggest that A-4 and A-5, like HC-3, inhibit the SDHACU, competitively and reversibly.
Details
- Title: Subtitle
- Characterization of the effect of two 4-methyl piperidine derivatives of hemicholinium-3, A-4 and A-5, on choline transport
- Creators
- Kimberly Y Sheff - Department of Pharmacology, College of Medicine, University of Iowa Diabetes Endocrinology Research Center, Iowa CityMark A YorekJohn P Long
- Resource Type
- Journal article
- Publication Details
- The Journal of pharmacology and experimental therapeutics, Vol.255(1), pp.357-363
- DOI
- 10.1016/S0022-3565(25)12783-3
- PMID
- 2213567
- ISSN
- 0022-3565
- eISSN
- 1521-0103
- Grant note
- NS-23785 / NINDS NIH HHS AM25295 / NIADDK NIH HHS
- Language
- English
- Date published
- 10/1990
- Academic Unit
- Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984094615702771
Metrics
18 Record Views