Influence of histamine H3-antagonists on human leukocytes

Abstract

To determine the role of the histamine H3-receptor on basophils, different specific H3-antagonists were investigated. Incubation of washed leukocytes with N alpha-acylated histamine-derivatives (N alpha-ahd) induced elevated histamine levels. This process turned out to be dependent on dose, time and temperature, but independent of Ca2+ and Mg2+ ions. IgE-mediated histamine release was not modulated. [3H]-L-histidine was not decarboxylated into [3H]-histamine in spite of the observed histamine increase. Highly purified basophils did not show any histamine elevation but purified neutrophils and eosinophils were found to have increased histamine levels even after disintegration and subsequent incubation with N alpha-ahd. It seems that the increased histamine levels result from the cleavage of the applied histamine amides. Other potent H3-antagonists (e.g. thioperamide) neither produced increased histamine levels nor influenced IgE-mediated release from basophil leukocytes. The existence of H3-receptors on human basophils therefore seems unlikely.

The intradermal effects of the H3 receptor agonist R α methylhistamine in human skin

“…The effect of RAMHA and thioperamide on histamine release from human adenoidal mast cells has been studied. 17 RAMHA had no effect, but thioperamide increased spontaneous and decreased concanavalin Ainduced histamine release. Its spontaneous histaminereleasing effect was thought to indicate the presence of the H 3 receptor, but the differing effects on stimulated and unstimulated cells suggested that H 3 -independent mechanisms may be involved.…”

Histamine up-regulates phosphodiesterase 4 activity and reduces prostaglandin E 2 -inhibitory effects in human neutrophils

“…Consistent with these reports, we found that cimetidine, an H 2 -histamine receptor antagonist, abolished the increased expresion of PDE4B induced by histamine whilst dexchlorpheniramine, an H 1 -antihistamine, was not effective. H 3 -histamine receptor antagonists were not tested since the existence of this class of histamine receptors on human neutrophils seems unlikely [43,44] In addition, we examined whether the up-regulation by histamine of PDE4 activity in human neutrophils had an impact on their functional responsiveness to a different autacoid, PGE 2 , which also acts by increasing cAMP in human neutrophils following stimulation of EP 2 receptors coupled to adenylyl cyclase [45]. As demonstrated in concentrationresponse studies, pretreatment of cells with histamine substantially decreased the ability of PGE 2 to inhibit the SOZ-induced release of superoxide anion.…”

Human mast cells and basophils—How are they similar how are they different?

“…The H2R‐mediated inhibitory actions of histamine is more prominent in basophils than in mast cells . H3R does not seem to affect basophil functions . H4R expression has been shown on human mast cells and basophils .…”

“…[159][160][161] H3R does not seem to affect basophil functions. 162,163 H4R expression has been shown on human mast cells and basophils. 164,165 H4R activation can modulate the function of mast cells and basophils.…”