Characterization of histamine H1 binding sites on human T lymphocytes by means of 125I-iodobolpyramine. Preferential expression of H1 receptors on CD8 T lymphocytes.
The presence of histamine H1 receptors on lymphocytes has been indirectly suggested by the various effects of agonists or antagonists on the functionally distinct T lymphocyte subsets. Recently, a new H1 antagonist, 125I-iodobolpyramine, whose structure is similar to mepyramine, has become available for the detection of H1 receptors in guinea pig brain. When using 125I-iodobolpyramine on human T lymphocytes, the presence of a single highly specific H1 binding site was evidenced. The binding of 125I-iodobolpyramine to human T cells was reversible when using 1000-fold excess of the cold H1 antagonist, d-chlorpheniramine. Binding saturation was achieved at 0.60-0.65 nM of 125I-iodobolpyramine, the binding equilibrium was reached in 20-30 min at 27 degrees C. The dissociation constant was KD = 0.41 +/- 0.07 (mean +/- SE) and the number of receptors per T cell was 3407 +/- 592 (mean +/- SE) as deduced from saturation and kinetic curves. In competition experiments using a panel of H1 ligands, the T cell binding sites detected by 125I-iodobolpyramine showed a pharmacological behavior characteristic of histamine H1 receptors. It was of particular interest that 125I-iodobolpyramine binding displayed clearcut stereoselectivity as assessed by the higher affinity of the d-configuration of chlorpheniramine than the l form. Study of purified CD4 and CD8 T cells showed that twice as much H1 histamine receptors were expressed by CD8 T lymphocytes (6615 +/- 1125) as compared to CD4 T cells (3545 +/- 459). These results underline the need for studying the functional properties of such pharmacologically defined T lymphocyte H1 binding sites.
Villemain
F M
FM
INSERM U25-CNRS LA 122, Hôpital Necker, Paris, France.
Bach
J F
JF
Chatenoud
L M
LM
D000631:Aminopyridines / Q000378:metabolism*; D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D016827:CD8 Antigens; D002462:Cell Membrane / Q000378:metabolism; D002531:Cerebellum / Q000378:metabolism; D006168:Guinea Pigs; D006801:Humans; D007700:Kinetics; D011738:Pyrilamine / Q000031:analogs & derivatives / Q000378:metabolism*; D011969:Receptors, Histamine H1 / Q000378:metabolism*; D013388:Succinimides / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism
D000631:Aminopyridines; D000945:Antigens, Differentiation, T-Lymphocyte; D016827:CD8 Antigens; D011969:Receptors, Histamine H1; D013388:Succinimides; C048171:iodobolpyramine; D011738:Pyrilamine