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  • Title: Effects of verapamil, diltiazem, nisoldipine and felodipine on sarcoplasmic reticulum.
    Author: Wang T, Tsai LI, Schwartz A.
    Journal: Eur J Pharmacol; 1984 May 04; 100(3-4):253-61. PubMed ID: 6234179.
    Abstract:
    Verapamil, diltiazem, nisoldipine and felodipine, calcium antagonist drugs with different chemical structures, were studied for their effects on activities of sarcoplasmic reticulum (SR) isolated from dog cardiac and rabbit skeletal muscles. Nisoldipine and felodipine exerted biphasic actions on both cardiac and skeletal SR Ca2+-ATPase with maximum activation of 40-60% occurring at 20-40 microM for nisoldipine and 30-40% occurring at 15-30 microM for felodipine. At higher drug concentrations, Ca2+-ATPase was inhibited. In the presence of oxalate the maximum activation of the Ca2+ uptake rates at 5-20 microM nisoldipine were 30-50% for cardiac SR and at 80-100 microM of the drug were 300-500% for skeletal SR. Felodipine inhibited the rate of Ca2+ uptake by dog cardiac SR, but activated Ca2+ uptake by rabbit skeletal SR with a maximum of 30-50% at 12-25 microM. At higher concentrations of the two drugs the rate of Ca2+ uptake was inhibited. In the absence of oxalate, i.e., limited transport, nisoldipine shortened the duration of time that Ca2+ was bound to the cardiac and skeletal SR, while the rate of release of Ca2+ from skeletal SR was stimulated. Felodipine at low concentrations similarly caused a premature release of Ca2+ from skeletal SR at a rapid rate; at high concentrations both drugs did not alter Ca2+ binding but delayed Ca2+ release. Unlike nisoldipine and felodipine, verapamil and diltiazem inhibited the rates of Ca2+ transport both in cardiac and skeletal SR. The two drugs inhibited Ca2+-ATPase in cardiac SR but activated the enzyme in skeletal SR.(ABSTRACT TRUNCATED AT 250 WORDS)
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