Mechanism of histamine release induced by levofloxacin, a fluoroquinolone antibacterial agent.
The present study was designed to clarify the mechanism of histamine release caused by levofloxacin, a fluoroquinolone antibacterial agent, using rat peritoneal mast cells. Levofloxacin induced a concentration-dependent histamine secretion from 300 microg/ml without lactate dehydrogenase leakage, and the release was rapidly completed within 30 s. This action was dependent on temperature, energy, pH and intracellular Ca(2+), similarly to the effect of compound 48/80, a basic compound. Unlike that with the calcium ionophore A23187, histamine secretion due to levofloxacin or compound 48/80 was prevented by pretreatment with either pertussis toxin or benzalkonium chloride, a selective inhibitor of G proteins of G(i) subtypes. Moreover, the histamine release elicited by levofloxacin or compound 48/80 was suppressed by hydrolysis of sialic acid residues on the cell surface brought about by neuraminidase. These results demonstrate that the mechanism by which levofloxacin exerts histamine release may be closely linked to activation of pertussis toxin-sensitive G proteins.
Mori
K
K
Drug Safety Research Laboratory, Daiichi Pharmaceutical Co., Ltd., 16-13 Kitakasai 1-chome, Edogawa-ku, Tokyo, Japan. morikslf@daiichipharm.co.jp
Maru
C
C
Takasuna
K
K
Furuhama
K
K
D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001548:Benzalkonium Compounds / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology; D006636:Histamine Release / Q000187:drug effects*; D006863:Hydrogen-Ion Concentration; D064704:Levofloxacin; D008297:Male; D009439:Neuraminidase / Q000494:pharmacology; D015242:Ofloxacin / Q000494:pharmacology*; D037342:Pertussis Toxin; D051381:Rats; D017207:Rats, Sprague-Dawley; D013696:Temperature; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000890:Anti-Infective Agents; D001548:Benzalkonium Compounds; D010566:Virulence Factors, Bordetella; D064704:Levofloxacin; D015242:Ofloxacin; D037342:Pertussis Toxin; D009439:Neuraminidase; D019204:GTP-Binding Proteins; D002118:Calcium