Binding of histamine H3-receptor antagonists to hematopoietic progenitor cells. Evidence for a histamine transporter unrelated to histamine H3 receptors.
Hematopoietic progenitor cells can take up histamine or release IL-3-induced histamine through a bi-directional transport system that is blocked by H3-receptor antagonists. In the present study we demonstrate a correlation between the affinity of various H3-receptor antagonists and their potency as inhibitors of histamine uptake. All compounds that blocked histamine uptake also inhibited IL-3-induced histamine release. Yet, classical H3 receptors are not involved in this biological activity, since highly specific histamine H3-receptor agonists neither alter histamine uptake nor affect the release of endogenous histamine synthesized in response to IL-3. Furthermore, the inhibitory effect of H3-receptor antagonists on histamine uptake was not reversed by the agonists. Unlike H3-receptor antagonists, the agonists did not displace the binding of the labeled antagonist iodoproxyfan.
Corbel
S
S
CNRS URA 1461, Hôpital Necker, Paris, France.
Traiffort
E
E
Stark
H
H
Schunack
W
W
Dy
M
M
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006632:Histamine / Q000378:metabolism*; D006633:Histamine Antagonists / Q000378:metabolism* / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D018100:Receptors, Histamine H3 / Q000378:metabolism*; D013379:Substrate Specificity
D002352:Carrier Proteins; D006633:Histamine Antagonists; D018100:Receptors, Histamine H3; D006632:Histamine