Possible Participation of Histamine H3-Receptors in the Regulation of Anaphylactic Histamine Release from Isolated Rat Peritoneal Mast Cells

Abstract

ABSTRACT-Anaphylactic histamine release from isolated rat peritoneal mast cells was concentration dependently blocked by a 5-min treatment with exogenous histamine at 0.9 and 9 pM and enhanced by a 20 to 30-min treatment with thioperamide (H3-antagonist) at 3 pM with significance, but little affected by mepyramine (H,-antagonist) and cimetidine (H2-antagonist) at the cell concentration of 106 mast cells/ml. At a low concentration of mast cells (104 mast cells/ml), (R)-a-methylhistamine (a-MH), an H3-agonist, at 0.9-90 pM also inhibited the release in a concentration-dependent fashion. Thioperamide, but neither mepyramine nor cimetidine, significantly restored the decreased release by a-MH. However, the complete restoration by thioperamide could not be achieved because the drug itself slightly but concentration dependently inhibited anaphylactic histamine release. On the other hand, not only betahistine and dimaprit but also a-MH did not suppress histamine release from the mast cells induced by compound 48/80. In rat plasma, considerable levels of histamine were detected. From these results, it is strongly suggested that histamine H3-like receptors are largely responsible for the negative feedback regulation of the anaphylactic histamine release from rat peritoneal mast cells. In the early 1980s, a third receptor of histamine was identified, which regulates the synthesis and release of histamine in the histaminergic nerve ends in the rat brain, and this was designated as the H3-receptor (1).Since then, the development of specific and selective agonists and antagonists of histamine receptor subtypes has revealed that H3-receptors exist in other tissues in cluding the ileum (2), airway (3, 4) and blood vessels (5); this was concluded from the observations that the neural stimulation-induced twitch responses of these tissues are inhibited by modulation of ACh, neuropeptides and other neurotransmitter release by H3-receptor stimula tion, in a similar manner to that of the rat cerebral cortex. Thus, the majority of the investigations on H3-receptors were initially focused on the modulation of neurotrans mitter release and/or histamine synthesis in the presynap tic ends of the brain or other tissues. In addition, there have recently been a number of reports on the roles of the receptor in effector organs: H3-receptor stimulation relaxed rabbit middle cerebral artery preconstricted with K+ by acceleration of nitric oxide and prostacyclin forma tion from the endothelium (6, 7); an H3-antagonist aggra vated experimental allergic asthma in the guinea pig (8); an H3-agonist and H3-antagonist inhibited and enhanced, respectively, the histamine release from isolated gastric glands (9), and H3-receptor stimulation specifically down regulated histamine synthesis in isolated fundic mucosal cells (10) in rabbits; an H3-receptor agonist reduced gas trin-induced vascular histamine release in the isolated rat stomach (11).In the present study, we obtained evidence indicating that isolated rat peritoneal mast cells have surface H3 re...

Characterization of purification-associated reduction in IgE-dependent histamine release from rat peritoneal mast cells

“…In 1992, Mackay and Pearce reported that anti-IgE-and ConA-induced histamine release was reduced after mast cell purification [19]. Furthermore, Kohno et al confirmed that antigeninduced histamine release was also reduced after purification [20]. These results clearly indicate that purificationassociated reduction of histamine release is a specific phenomenon for IgE-dependent mast cell activation.…”

Histamine H4Receptor Mediates Chemotaxis and Calcium Mobilization of Mast Cells

“…In the literature, it has been unclear whether mast cells express the H 3 receptor. Most studies used thioperamide as a specific H 3 antagonist (Kohno et al, 1994;Bissonnette, 1996), but recent data indicate that both the mouse and human H 4 receptor can bind thioperamide as well (Liu et al, 2001b). It is therefore likely that the effects of histamine on mast cells that can be blocked by thioperamide are actually mediated by H 4 receptors.…”

Recovery of Purification-Associated Reduction in Antigen-Induced Histamine Release from Rat Peritoneal Mast Cells.

“…Purified peritoneal mast cells of rats usually release a small amount of histamine upon IgE-dependent stimulation, [19][20][21][22][23] therefore, investigators have sometimes employed phosphatidylserine to potentiate the response. [28][29][30] Previously, we demonstrated that the low IgE-dependent histamine release from purified mast cells could be recovered or potentiated by reconstitution with separated non-mast cells.…”

“…[19][20][21] Contact of mast cells with purification media does not result in the reduced histamine release, but the purification itself is crucial. Furthermore, the reduction of histamine release from purified mast cells seems to be a specific phenomenon for IgE-dependent mast cell activation, and the reduced histamine release is recovered by reconstituting with non-mast cells separated from mast cells.…”

“…[14][15][16][17][18] It has been noticed, however, that rat peritoneal mast cells purified by density gradient centrifugation release only a small amount of histamine upon challenge with antigen in comparison with non-purified preparations. [19][20][21] Contact of mast cells with purification media does not result in the reduced histamine release, but the purification itself is crucial. Furthermore, the reduction of histamine release from purified mast cells seems to be a specific phenomenon for IgE-dependent mast cell activation, and the reduced histamine release is recovered by reconstituting with non-mast cells separated from mast cells.…”