Leukotriene B4 induced steady state calcium rise and superoxide anion generation in guinea pig eosinophils are not related events.
We have examined the nature of the leukotriene B4 (LTB4) induced steady state intracellular calcium rise [Ca++]i in guinea pig eosinophils and the relationship between LTB4 induced [Ca++]i and superoxide anion (O2-). LTB4 induced a rise in intracellular Ca++ (following a Ca(++)- transient) in a dose dependent manner with an optimal increase around 50-100 nM. Depolarizing concentrations of K+ did not induce [Ca++]i in eosinophils nor did the voltage operated calcium channel inhibitor, nifedipine, inhibit the LTB4 induced Ca++ entry. In contrast, SK&F 96365 a purported receptor operated calcium channel (ROCC) inhibitor, and its parent compound SC 32849, attenuated LTB4 induced [Ca++]i. Five reference anti-asthmatics (ketotifen, formoterol, disodium-cromoglycate, theophylline and budesonide) had no influence on LTB4 induced [Ca++]i. LTB4 also induced O2- generation (a functional response) in a dose dependent manner with optimal effect around 100 nM. However, in contrast to Ca(++)- influx, LTB4 induced O2- generation was not affected by either SK&F 96365 or its analogues or reference anti-asthmatics. The results of this study suggest a) the presence of a non-voltage gated, receptor operated, calcium sequestration process in guinea pig eosinophils, b) that LTB4 induced [Ca++]i and O2- generation are apparently unrelated events in these cells, and c) that standard anti-asthmatics do not have an influence on either LTB4 induced [Ca++]i or O2- generation in these cells.
Subramanian
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CIBA-GEIGY Ltd. Research Department, Pharmaceuticals Division, Basel, Switzerland.
D000818:Animals; D000838:Anions; D002118:Calcium / Q000378:metabolism*; D004804:Eosinophils / Q000378:metabolism*; D005456:Fluorescent Dyes; D016257:Fura-2; D006168:Guinea Pigs; D007093:Imidazoles / Q000494:pharmacology; D007975:Leukotriene B4 / Q000494:pharmacology*; D008297:Male; D010529:Peritoneal Cavity / Q000166:cytology; D011188:Potassium / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism*
D000838:Anions; D005456:Fluorescent Dyes; D007093:Imidazoles; D013481:Superoxides; D007975:Leukotriene B4; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D011188:Potassium; D002118:Calcium; D016257:Fura-2