Does intracellular histamine mediate mast cell histamine release?
Previously, we demonstrated that through binding a novel intracellular receptor of microM affinity (HIC), histamine mediates, and the HIC antagonist N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine. HCl (DPPE) inhibits, platelet aggregation and serotonin granule secretion; the latter response is dependent upon the same processes that mediate histamine release from mast cell granules. We now show that, as for platelet serotonin release, DPPE blocks concanavalin A-stimulated mast cell histamine release with a potency (IC50 = 30 microM) greater than the H1-antagonist, pyrilamine (IC50 = 150 microM) or the H2-antagonist cimetidine (IC50 = 5 mM), correlating with rank order of potency to inhibit 3H-histamine binding in rat brain membranes and liver microsomes. We postulate that histamine release from mast cells is mediated at HIC by second messenger intracellular histamine. However, unlike platelets, mast cells do not appear to rely on newly synthesized histamine. Rather, as for calcium, histamine may be mobilized from bound stores to mediate histamine secretion.
Department of Medicine, University of Manitoba, Winnipeg, Canada.
L J
LJ
Brandes
B
B
Sukhu
R P
RP
Bogdanovic
D000818:Animals; D002463:Cell Membrane Permeability; D002927:Cimetidine / Q000494:pharmacology; D003208:Concanavalin A / Q000494:pharmacology*; D006632:Histamine / Q000502:physiology*; D006636:Histamine Release / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology*; D010718:Phosphatidylserines / Q000494:pharmacology; D011738:Pyrilamine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012503:Saponins
D010718:Phosphatidylserines; D012503:Saponins; D003208:Concanavalin A; D002927:Cimetidine; D006632:Histamine; D011738:Pyrilamine