Effect of nisoldipine on priming and activation of the human neutrophil respiratory burst

A. B. Karnad, K. L. Hartshorn, A. I. Tauber

Research output: Contribution to journalLetter

4 Scopus citations

Abstract

Nisoldipine inhibits calcium (Ca++) influx in human neutrophils: Preincubation with the dihydropyridine, nisoldipine (1.5 μM) resulted in a 30% decrease in[45]Ca++ influx during formyl-methionineleucine-phenylalanine (FMLP) stimulation in primed as well as resting cells. Although the drug does not inhibit Ca++ dependent effector functions elicited by FMLP, e.g. superoxide (O2-) production, it inhibits FMLP priming, a phenomenon that is independent, of extracellular Ca++. Nisoldipine, exhibited a narrow dose response with an ED50 of ca. 1 μM and total inhibition of primed O2/- response at 1.5 μM. Nisoldipine (1.5 μM) also abolished the incremental rise of Ca++i in primed neutrophils stimulated with FMLP. The dissociation of nisoldipine inhibitory effects on cell effector function and Ca++ transport were corroborated in studies with neutrophils stimulated with influenza virus and phorbol myristate acetate (PMA), stimuli which do not exhibit an extracellular Ca++-dependence in their elicited responses. Unlike in FMLP-stimulated cells, nisoldipine reduced influenza virus and PMA initiated respiratory burst, indicating that this drug has inhibitory effects on neutrophil function independent of its effect on Ca++ metabolism. Possible sites of action are postulated at phospholipase A2 or calmodulin-regulated activities. Caution is thus required in interpreting the effects of dihydropyridine on cell function, when the drug is used at micromolar concentration.

Original languageEnglish (US)
Pages (from-to)79-85
Number of pages7
JournalAgents and Actions
Volume31
Issue number1-2
DOIs
StatePublished - Aug 1990
Externally publishedYes

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology (medical)

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