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Isradipine inhibits PMN leukocyte function. A possible interference with the adenosine system
P L Capecchi1, F Laghi Pasini, L Ceccatelli
1Institute of Clinical Medicine, University of Siena School of Medicine, Policlinico Le Scotte, Italy.
Immunopharmacology and Immunotoxicology
|March 1, 1993
Summary
Isradipine, a dihydropyridine derivative, inhibits polymorphonuclear (PMN) leukocyte function and calcium influx. This cell-protective activity suggests its potential use in ischemia and reperfusion injury where PMN leukocytes cause tissue damage.
Area of Science:
- Pharmacology
- Cell Biology
- Immunology
Background:
- Polymorphonuclear (PMN) leukocytes play a critical role in tissue injury during ischemia and reperfusion.
- PMN leukocyte activation leads to enzyme release and free radical generation, contributing to pathogenesis.
- Calcium influx is a key event in PMN leukocyte activation and function.
Purpose of the Study:
- To investigate the effects of the dihydropyridine derivative isradipine on PMN leukocyte function.
- To explore the potential role of the adenosine system in isradipine's inhibitory effects.
- To evaluate isradipine's cell-protecting activity for potential therapeutic applications.
Main Methods:
- Assessment of PMN leukocyte enzyme release and free radical generation.
- Measurement of intracellular calcium influx using the fluorescent dye FURA 2/acetoxymethylester.
- Evaluation of the effect of the adenosine receptor antagonist theophylline on isradipine's activity.
Main Results:
- Isradipine significantly inhibited PMN leukocyte function, including enzyme release and free radical generation.
- Isradipine effectively prevented calcium influx into PMN leukocytes.
- Theophylline partially reversed isradipine's inhibitory effects, suggesting interaction with the adenosine system.
Conclusions:
- Isradipine exhibits significant PMN leukocyte inhibitory and cell-protecting properties.
- The findings suggest a potential interaction between isradipine and the adenosine system.
- Isradipine's demonstrated activities provide a rationale for its use in conditions involving PMN leukocyte-dependent tissue injury, such as ischemia-reperfusion damage.