Wittmann, Sigrid and Froehlich, Dieter and Daniels, Stephen (2002) Characterization of the human fMLP receptor in neutrophils and in Xenopus oocytes. BRITISH JOURNAL OF PHARMACOLOGY, 135 (6). pp. 1375-1382. ISSN 0007-1188
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1 N-Formyt peptides (e.g. fMLP; N-formyl-L-methionyl-L-leucyl-phenylalanine) are potent mediators for inflammatory reactions, We report functional expression in Xenopus oocytes of human fMLP-R98 cDNA, without co-expression of the promiscuous G-protein subunit, Galpha-16. 2 Stimulation of voltage-clamped oocytes (-70 mV) with fMLP produced a dose-dependent biphasic inward current with fast and slow components. Analysis using GTP-gamma-S and cholera and pertussis toxins suggested these currents are mediated by an endogenous G-protein of the Gq family. 3 The fast current reversed at -25 mV and was blocked by SITS (4-acetamido-4'-isothiocyana-tostilbene-2,2'-disulphonic acid), suggesting the current is carried by Cl-. The slow current showed weak inward rectification, was Ca2+-dependent and blocked by Cd2+, 4-AP (4-aminopyridine) and haloperidol, suggesting activation of a mixed population of cation channels. 4 Comparative experiments with human neutrophils using flow cytometric analysis showed that the proportion of neutrophils activated by fMLP was reduced in the presence of SITS, in the absence of external calcium and in the presence of Cd2+, TEA (tetraethylammonium) and haloperidol but not 4-AP. In addition, the oxidative burst from activated neutrophils was reduced by SITS and by the absence of external calcium but not by Cd2+, TEA, 4-AP or haloperidol. 5 We suggest that in human neutrophils activation by fMLP is dependent on store-operated calcium influx that appears to be regulated by Cl- channels and linked, in part, to non-selective cation channels.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | FORMYL PEPTIDE RECEPTOR; PROTEIN-COUPLED RECEPTORS; SIGNAL-TRANSDUCTION; LAEVIS OOCYTES; FORMYLPEPTIDE RECEPTOR; FUNCTIONAL EXPRESSION; OXIDATIVE RESPONSE; POTASSIUM CURRENT; CHANNELS; CELLS; fMLP; Xenopus oocytes; neutrophil; non-selective cation channel; chloride channel |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Anästhesiologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 08 Nov 2021 10:20 |
| Last Modified: | 08 Nov 2021 10:20 |
| URI: | https://pred.uni-regensburg.de/id/eprint/40490 |
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