Abstract |
1. Selected Ca-channel antagonists were tested at 20 microM as inhibitors of Ca(2+)-uptake in human sickle red cells. Nitrendipine, fendiline, and bepridil (and its stereoisomers), were found to be as effective as methoxyverapamil (D-600) in inhibiting a fraction (25%) of Ca(2+)-uptake. In contrast cetiedil and Org 30701 were ineffective. 2. The drugs were subsequently tested as inhibitors of Ca(2+)-induced K+ efflux (Gardos) from sickle cells. They all showed inhibitory activity, with the order of efficacy nitrendipine greater than fendiline greater than bepridil greater than cetiedil greater than Org 30701. 3. With a 15 h programme of deoxygenation/reoxygenation cycles in a gas exchanger, it was shown that the inhibitors protected against cellular dehydration and loss of filterability in the order nitrendipine greater than fendiline greater than bepridil greater than cetiedil greater than Org 30701. However, significant stomatocytosis occurred at high concentrations of cetiedil, and bepridil (including its stereoisomers and analogues) impairing cell deformability. 4. It is concluded that Ca-antagonists may partially block both Ca(2+)-uptake and Ca(2+)-induced K+ efflux. The latter pathway is significant in contributing to sickle cell dehydration and nitrendipine is the most effective inhibitor of this route.
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Authors | J C Ellory, G B Nash, P C Stone, S J Culliford, E Horwitz, J Stuart |
Journal | British journal of pharmacology
(Br J Pharmacol)
Vol. 106
Issue 4
Pg. 972-7
(Aug 1992)
ISSN: 0007-1188 [Print] England |
PMID | 1393295
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Azepines
- Calcium Channel Blockers
- Potassium Channels
- cetiedil
- Bepridil
- Nitrendipine
- Fendiline
- Oxygen
- Calcium
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Topics |
- Anemia, Sickle Cell
(blood)
- Azepines
(pharmacology)
- Bepridil
(pharmacology)
- Calcium
(blood, pharmacology)
- Calcium Channel Blockers
(pharmacology)
- Erythrocytes, Abnormal
(drug effects)
- Fendiline
(pharmacology)
- Humans
- In Vitro Techniques
- Nitrendipine
(pharmacology)
- Oxygen
(metabolism)
- Potassium Channels
(drug effects)
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