ArticleBritish journal of pharmacology2004
Molecular mechanisms of vasoselectivity of the 1,4-dihydropyridine lercanidipine.
Article in British journal of pharmacology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
3 citing papers in PubMed, 13 citations in OpenAlex.
- New Insights into the Nephroprotective Potential of Lercanidipine.International journal of molecular sciences · 2023Review
- Article
- Lercanidipine in hypertension.Vascular health and risk management · 2005Review
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
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Abstract
The effects of (S)- and (R)-lercanidipine on CHO cells stably expressing the cardiac (Ca(v)1.2a) or vascular (Ca(v)1.2b) splice variant of the L-type calcium channel pore subunit were studied, using whole-cell and single-channel patch-clamp measurements. Lercanidipine block of Ca(v)1.2b current was enantioselective. (S)-lercanidipine was 4.1-fold more potent. Experiments using acidic solutions (pH 6.8) revealed a 6.4-fold enhanced inhibitory effect of (S)-lercanidipine compared with physiological conditions (pH 7.4) indicating that the charged form mediates inhibition. At depolarised holding potential (-40 mV), (S)-lercanidipine exhibited a 35-fold greater potency, compared with standard conditions (-80 mV). A comparison of the concentration-dependent inhibition of Ca(v)1.2a with Ca(v)1.2b subunit currents by (S)-lercanidipine revealed only a 1.8-fold difference in IC(50), but the slope of the dose-response curve was much steeper (n(H)=2.3) with Ca(v)1.2a, compared with Ca(v)1.2b (n(H)=0.8). This indicates overlap between agonistic and antagonistic effects, predominant with the cardiac Ca(v)1.2a subunit. This idea is supported by transient stimulatory effects, and a slight leftward shift of the IV curves. These effects were more prominent for Ca(v)1.2a than for Ca(v)1.2b. Single-channel experiments confirmed typical features of calcium channel agonists such as prolonged channel openings, a component of lengthened openings, and an enhanced open probability in the presence of (S)-lercanidipine. Again, these findings were concentration-dependent and more pronounced for Ca(v)1.2a than for Ca(v)1.2b. Our data indicate a splice-variant predominant agonism as a new mechanism contributing to the vasoselectivity of lercanidipine, along with marked voltage-dependence of action.
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