TY - JOUR
T1 - Effects of manidipine and nitrendipine enantiomers on the plateau phase of K+-induced intracellular Ca2+ increase in GH3 cells
AU - Cataldi, Mauro
AU - Taglialatela, Maurizio
AU - Palagiano, Francesco
AU - Secondo, Agnese
AU - De Caprariis, Paolo
AU - Amoroso, Salvatore
AU - Di Renzo, Gianfranco
AU - Annunziato, Lucio
PY - 1999/7/2
Y1 - 1999/7/2
N2 - 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.
AB - 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.
KW - Ca channel, voltage sensitive
KW - Ca concentration, intracellular
KW - Chirality
KW - Dihydropyridine
KW - Manidipine
KW - Nitrendipine
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UR - http://www.scopus.com/inward/citedby.url?scp=0032990812&partnerID=8YFLogxK
U2 - 10.1016/S0014-2999(99)00149-1
DO - 10.1016/S0014-2999(99)00149-1
M3 - Article
C2 - 10440102
AN - SCOPUS:0032990812
VL - 376
SP - 169
EP - 178
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
IS - 1-2
ER -