Inhibitory effects of phenyltin compounds on stimulus-induced changes in cytosolic free calcium and plasma membrane potential of human neutrophils.
To clarify the inhibitory mechanisms by triphenyltin chloride (TPTCl) on superoxide anion formation in neutrophils, the effects of phenyltin compounds [TPTCl, diphenyltin dichloride (DPTCl2) and phenyltin trichloride (MPTCl3) on the increase of cytosolic free calcium and the changes in membrane potential in neutrophils stimulated by n-formyl-methionyl-leucyl-phenylalanine (FMLP) were examined. TPTCl and DPTCl2 concentration dependently inhibited the increase of fluorescence intensity of the dye 3,3'-dipropyl-thiodicarbocyanine iodide [diS-C3-(5)] (membrane potential probe) in neutrophils induced by 0.1 microM FMLP in the presence or absence of extracellular calcium (1.26 mM). TPTCl had a greater inhibitory effect on FMLP-mediated membrane potential change than that of DPTCl2. In the presence of extracellular calcium, TPTCl and DPTCl2 increased intracellular free calcium [( Ca2+]i) of unstimulated fura-2-loaded neutrophils at concentrations from 1.0 to 10 microM TPTCl and from 2.5 to 10 microM DPTCl2. TPTCl and DPTCl2 also increased slightly, in the absence of extracellular calcium, [Ca2+]i without stimulation of FMLP in neutrophils. However, TPTCl and DPTCl2 significantly inhibited the rise of [Ca2+]i in neutrophils stimulated by FMLP at concentrations from 2.5 microM to 10 microM TPTCl and at a concentration of 10 microM DPTCl2 in the absence of extracellular calcium. TPTCl and DPTCl2 significantly inhibited the superoxide anion production by FMLP at concentrations over 2.5 microM in the presence of extracellular calcium. In the absence of extracellular calcium, TPTCl and DPTCl2 also inhibited the superoxide anion production by FMLP at concentrations over 1.5 microM TPTCl and over 5.0 microM DPTCl2.(ABSTRACT TRUNCATED AT 250 WORDS)
Miura
Y
Y
Department of Hygiene, Dokkyo University School of Medicine, Tochigi, Japan.
Matsui
H
H
D052160:Benzothiazoles; D002118:Calcium / Q000378:metabolism*; D002232:Carbocyanines / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects; D002470:Cell Survival; D003600:Cytosol / Q000378:metabolism*; D005456:Fluorescent Dyes; D016257:Fura-2 / Q000494:pharmacology; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects*; D009947:Organotin Compounds / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism
D052160:Benzothiazoles; D002232:Carbocyanines; D005456:Fluorescent Dyes; D009947:Organotin Compounds; D013481:Superoxides; C012944:3,3'-dipropyl-2,2'-thiadicarbocyanine; D009240:N-Formylmethionine Leucyl-Phenylalanine; C012594:triphenyltin chloride; D002118:Calcium; D016257:Fura-2