2-Benzyloxybenzaldehyde inhibits formyl peptide-stimulated increase in intracellular Ca2+ in neutrophils mainly by blocking Ca2+ entry.
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.
Wang
Jih-Pyang
JP
Department of Education and Research, Taichung Veterans General Hospital, Taichung, Taiwan; Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung, Taiwan, ROC. w1994@vghtc.gov.tw
Chang
Ling-Chu
LC
Kuan
Yu-Hsiang
YH
Tsao
Lo-Ti
LT
Huang
Li-Jiau
LJ
Kuo
Sheng-Chu
SC
D000818:Animals; D001547:Benzaldehydes / Q000494:pharmacology*; D002118:Calcium / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007424:Intracellular Fluid / Q000187:drug effects* / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
C468728:2-benzyloxybenzaldehyde; D001547:Benzaldehydes; D009240:N-Formylmethionine Leucyl-Phenylalanine; D002118:Calcium