Effects of manidipine and nitrendipine enantiomers on the plateau phase of K+-induced intracellular Ca2+ increase in GH3 cells

Mauro Cataldi, Maurizio Taglialatela, Francesco Palagiano, Agnese Secondo, Paolo De Caprariis, Salvatore Amoroso, Gianfranco Di Renzo, Lucio Annunziato

Research output: Contribution to journalArticlepeer-review

Abstract

The aim of the present study was to investigate whether the chirality and type of substitution at position 3 of the dihydropyridine ring influences the pattern of voltage-gated Ca2+ channel blockade. For this purpose, the effect of R- and S-enantiomers of manidipine and nitrendipine, separated by chiral High-Pressure-Liquid-Chromatography columns, were investigated by fura-2 microfluorimetry during the plateau phase of the intracellular Ca2+ ([Ca2+](i)) increase induced by 55 mM K+ and by patch-clamp recording of Ca2+ channel activity in GH3 cells. R- and S-enantiomers of both nitrendipine and manidipine produced a [Ca2+](i) decay of the K+-induced plateau phase that followed a biexponential pattern with a 'fast' and a 'slow' phase. The S-configuration of both nitrendipine and manidipine produced a larger [Ca2+](i) decrease during the 'fast phase', and a faster and smaller [Ca2+](i) decrease in the 'slow phase' than did the R-enantiomers. The S- and R-enantiomers of manidipine, which possess a longer and more lipophilic side chain at position 3 of the dihydropyridine ring, induced a slower [Ca2+](i) decrease than that observed with the respective nitrendipine enantiomers. Accordingly, patch-clamp experiments revealed that the S-enantiomers of both dihydropyridines displayed a faster onset of action and produced a greater blockade than the R-enantiomers. These results suggest that the enantiomeric configuration and a small side chain at position 3 of the dihydropyridine ring are factors in the chemical structure which influence the pattern of blockade of voltage-sensitive Ca2+ channels. Copyright (C) 1999 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)169-178
Number of pages10
JournalEuropean Journal of Pharmacology
Volume376
Issue number1-2
DOIs
Publication statusPublished - Jul 2 1999

Keywords

  • Ca channel, voltage sensitive
  • Ca concentration, intracellular
  • Chirality
  • Dihydropyridine
  • Manidipine
  • Nitrendipine

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

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