Skip to main content
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1994 Mar;111(3):903–905. doi: 10.1111/j.1476-5381.1994.tb14823.x

Specific inhibition of Ca-activated K channels in red cells by selected dihydropyridine derivatives.

J C Ellory 1, S J Culliford 1, P A Smith 1, M W Wolowyk 1, E E Knaus 1
PMCID: PMC1910101  PMID: 8019767

Abstract

1. Thirty two dihydropyridine derivatives were screened as potential inhibitors of the Ca-activated K-channel in human red cells. 2. Three derivatives (26, 29, 32 see Tables 1 and 2) with high activity were then characterized in detail, and also tested against the smooth muscle Ca-channel and shown to have varying potencies. 3. One of the more potent derivatives (32) and nitrendipine were also tested on the Ca-activated K-channel, Maxi-K channel, from mouse pancreatic beta-cells. 4. We conclude from our results that it may be possible to develop selective Gardos-channel inhibitors based on these molecules, which may be of benefit in the treatment of sickle cell disease.

Full text

PDF
903

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Akula M. R., Matowe W. C., Wolowyk M. W., Knaus E. E. Synthesis and calcium channel antagonist activity of 3-arylmethyl 5-isopropyl 1,4-dihydro-2,6-dimethyl-4-(pyridyl)-3,5-pyridinedicarboxylates. Pharm Res. 1990 Sep;7(9):919–922. doi: 10.1023/a:1015941706008. [DOI] [PubMed] [Google Scholar]
  2. Akula M. R., Matowe W. C., Wolowyk M. W., Knaus E. E. Synthesis and calcium channel antagonist activity of alkyl cycloalkyl esters of nifedipine containing pyridinyl substituents. Drug Des Deliv. 1989 Dec;5(2):117–123. [PubMed] [Google Scholar]
  3. Akula M. R., Matowe W. C., Wolowyk M. W., Knaus E. E. Synthesis and calcium channel antagonist activity of nifedipine analogues containing 4-pyridyl and 3-arylethyloxycarbonyl substituents. Drug Des Deliv. 1990 Dec;7(1):11–17. [PubMed] [Google Scholar]
  4. Ashcroft F. M., Rorsman P. Electrophysiology of the pancreatic beta-cell. Prog Biophys Mol Biol. 1989;54(2):87–143. doi: 10.1016/0079-6107(89)90013-8. [DOI] [PubMed] [Google Scholar]
  5. Bokvist K., Rorsman P., Smith P. A. Block of ATP-regulated and Ca2(+)-activated K+ channels in mouse pancreatic beta-cells by external tetraethylammonium and quinine. J Physiol. 1990 Apr;423:327–342. doi: 10.1113/jphysiol.1990.sp018025. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bokvist K., Rorsman P., Smith P. A. Effects of external tetraethylammonium ions and quinine on delayed rectifying K+ channels in mouse pancreatic beta-cells. J Physiol. 1990 Apr;423:311–325. doi: 10.1113/jphysiol.1990.sp018024. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dagnino L., Li-Kwong-Ken M. C., Wolowyk M. W., Wynn H., Triggle C. R., Knaus E. E. Synthesis and calcium channel antagonist activity of dialkyl 1,4-dihydro-2,6-dimethyl-4-(pyridinyl)-3,5-pyridinedicarboxylates. J Med Chem. 1986 Dec;29(12):2524–2529. doi: 10.1021/jm00162a016. [DOI] [PubMed] [Google Scholar]
  8. Dagnino L., Li-Kwong-Ken M. C., Wynn H., Wolowyk M. W., Triggle C. R., Knaus E. E. Synthesis and calcium channel antagonist activity of dialkyl 4- (dihydropyridinyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinecarboxylates. J Med Chem. 1987 Apr;30(4):640–646. doi: 10.1021/jm00387a010. [DOI] [PubMed] [Google Scholar]
  9. Ellory J. C., Kirk K., Culliford S. J., Nash G. B., Stuart J. Nitrendipine is a potent inhibitor of the Ca(2+)-activated K+ channel of human erythrocytes. FEBS Lett. 1992 Jan 20;296(2):219–221. doi: 10.1016/0014-5793(92)80383-r. [DOI] [PubMed] [Google Scholar]
  10. GARDOS G. The function of calcium in the potassium permeability of human erythrocytes. Biochim Biophys Acta. 1958 Dec;30(3):653–654. doi: 10.1016/0006-3002(58)90124-0. [DOI] [PubMed] [Google Scholar]
  11. Kaji D. M. Nifedipine inhibits calcium-activated K transport in human erythrocytes. Am J Physiol. 1990 Aug;259(2 Pt 1):C332–C339. doi: 10.1152/ajpcell.1990.259.2.C332. [DOI] [PubMed] [Google Scholar]
  12. Latorre R., Oberhauser A., Labarca P., Alvarez O. Varieties of calcium-activated potassium channels. Annu Rev Physiol. 1989;51:385–399. doi: 10.1146/annurev.ph.51.030189.002125. [DOI] [PubMed] [Google Scholar]
  13. Ramesh M., Matowe W. C., Wolowyk M. W., Knaus E. E. Synthesis and calcium channel antagonist activity of alkyl t-butyl esters of nifedipine analogues containing pyridinyl substituents. Drug Des Deliv. 1987 Dec;2(2):79–89. [PubMed] [Google Scholar]
  14. Wynn H., Ramesh M., Matowe W. C., Wolowyk M. W., Knaus E. E. Synthesis and calcium channel antagonist activity of 1,2-dihydropyridyl analogues of nifedipine. Drug Des Deliv. 1988 Nov;3(3):245–256. [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES