title: Leukotriene B4 induced steady state calcium rise and superoxide anion generation in guinea pig eosinophils are not related events.
abstract: 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.
authors.affiliation: CIBA-GEIGY Ltd. Research Department, Pharmaceuticals Division, Basel, Switzerland.
authors.forename: N
authors.initials: N
authors.lastname: Subramanian
mesh_terms: 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*
chemical_list: 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