2-Benzyloxybenzaldehyde inhibits formyl peptide-stimulated increase in intracellular Ca2+ in neutrophils mainly by blocking Ca2+ entry

Naunyn Schmiedebergs Arch Pharmacol. 2004 Nov;370(5):353-60. doi: 10.1007/s00210-004-0993-7. Epub 2004 Oct 23.

Abstract

2-Benzyloxybenzaldehyde (CCY1a) inhibited the formyl-Met-Leu-Phe (fMLP)-induced elevation of cytosolic [Ca(2+)]() ([Ca(2+)](i)) in rat neutrophils. The late plateau phase, but not the initial Ca(2+) spike, of the fMLP-induced [Ca(2+)](i) change was inhibited by CCY1a. In the absence of external Ca(2+), CCY1a had no appreciable effect on either the fMLP- or cyclopiazonic acid (CPA)-induced [Ca(2+)](i) elevation. CCY1a failed to inhibit [Ca(2+)](i) changes induced by N-ethylmaleimide, GEA3162, ionomycin or sphingosine, but slightly inhibited the Ca(2+) signals elicited by ATP or interleukin-8 (IL-8). In a classical Ca(2+) readdition protocol, addition of CCY1a after cell activation strongly inhibited the [Ca(2+)](i) response to fMLP, whilst that to CPA was only slightly reduced. CCY1a nearly abrogated the fMLP-stimulated Mn(2+) influx but was less effective on the CPA-induced response. CCY1a attenuated the levels of tyrosine-phosphorylated bands in the 70-85 kDa molecular mass range. CCY1a had no effect on the basal [Ca(2+)](i) level, the pharmacologically isolated plasma membrane Ca(2+)-ATPase activity or on the mitochondrial membrane potential. Thus, CCY1a blocks fMLP-induced Ca(2+) entry into neutrophils probably by blocking the relevant Ca(2+) channel directly or, alternatively, indirectly through the attenuation of tyrosine phosphorylation of some cellular proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzaldehydes / pharmacology*
  • Calcium / antagonists & inhibitors
  • Calcium / metabolism*
  • Intracellular Fluid / drug effects*
  • Intracellular Fluid / metabolism
  • N-Formylmethionine Leucyl-Phenylalanine / antagonists & inhibitors
  • N-Formylmethionine Leucyl-Phenylalanine / pharmacology*
  • Neutrophils / drug effects*
  • Neutrophils / metabolism
  • Rats
  • Rats, Sprague-Dawley

Substances

  • 2-benzyloxybenzaldehyde
  • Benzaldehydes
  • N-Formylmethionine Leucyl-Phenylalanine
  • Calcium