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Specific binding sites for leukotriene B4 in guinea pig brain membranes

AJ de Brum-Fernandes, G Guillemette, P Borgeat and P Sirois

Department of Pharmacology, Faculty of Medicine, University of Sherbrooke, Quebec, Canada.

The presence of specific leukotriene B4 (LTB4) binding sites was investigated in membranes prepared from mouse, rat, guinea pig and rabbit brain. Specific binding sites have been found in guinea pig brain membranes (GPBM) but not in the other species studied. Specific binding of LTB4 to GPBM was proportional to membrane concentration, saturable and reversible, reaching a steady-state suggesting equilibrium after 30 min of incubation. Analysis of the binding data showed a single binding site with a Kd = 2.27 +/- 0.55 nM and a Bmax = 576 +/- 89.6 fmol/mg protein. The relative potencies of LTB4 analogs to displace the tritiated ligand were LTB4 greater than 20-hydroxy-LTB4 much greater than 20-carboxy-LTB4 greater than 12-(S)hydroxy- 5,8,10,14(Z,Z,E,Z)-eicosatetraenoic acid; LTD4 and LTC4 did not displace the ligand in concentrations up to 50 microM. The binding was inhibited by monovalent cations and GTP[gamma S] and increased by divalent cations. Specific binding was associated to the cerebral cortex. The present results suggest that these specific binding sites could represent functional LTB4 receptors in the guinea pig cerebral cortex with unknown biological effects.

Volume 259, Issue 3, pp. 1035-1042, 12/01/1991
Copyright © 1991 by American Society for Pharmacology and Experimental Therapeutics




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A Combinatorial G Protein-coupled Receptor Reconstitution System on Budded Baculovirus: EVIDENCE FOR G{alpha}i AND G{alpha}o COUPLING TO A HUMAN LEUKOTRIENE B4 RECEPTOR
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[Abstract] [Full Text] [PDF]


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Copyright © 1991 by the American Society for Pharmacology and Experimental Therapeutics.