INFLUENCE OF AMINOGLYCOSIDE ANTIBIOTICS, STREPTOMYCIN AND KANAMYCIN ON HISTAMINE SECRETION IN MAST CELLS

Abstract

Effects of kanamycin and streptomycin on histamine release from rat mast cells were examined in response of the cells to concanavalin A(Con A) plus phosphatidylserine (PS), phytohemagglutinin (PHA) plus PS or a mixture of low-molecular-weight polymers of P-methoxy-N-methylphenethylamine (compound 48/80). In the response to each of the above stimuli, kanamycin (20mM) or streptomycin (20mM) caused a decrease in the histamine release elicited in the presence of extracellular Ca^&lt2+&gt (1mM), although streptomycin showed the much higher inhibitory potency than kanamycin. Similarly, streptomycin was much more effective in suppressing compound 48/80-triggered histamine release in the absence of external Ca^&lt2+&gt. Histamine release in the absence of external Ca^&lt2+&gt in the response to the lectin plus PS diminished with increasing concentration of kanamycin, and in this respect streptomycin was much less effective. In the response to the lectin plus PS, external Ca^&lt2+&gt possessed potency to antagonize kanamycin (10mM)- or streptomycin (10mM)-caused inhibition of the histamine release, although more markedly the kanamycin-caused one. Streptomycin and kanamycin inhibit histamine release from mast cells challenged with IgE-directed secretagogue or compound 48/80, and the responsible mechanisms seem to implicate the Ca^&lt2+&gt-antagonistic action on the stimulus-provoked influx of Ca^&lt2+&gt and impairment of the cellular events linked to exocytosis.