CHARACTERIZATION OF HISTAMINE-RECEPTOR SUBTYPES REGULATING PROSTACYCLIN RELEASE FROM HUMAN ENDOTHELIAL-CELLS

1 The histamine receptor sub-types that are involved in the initiation and maintenance of prostacyclin (PGI2) release from human endothelial cells have been investigated. 2 Endothelial cells cultured from umbilical vein (HUVEC) were incubated with either histamine, the selective H-1-receptor agonists, 2-methyl histamine (2-MeHA) or thiazolylethylamine (ThEA), the H-1-agonist/H-3-antagonist, beta-histine (beta-His), the selective H-2-agonist, dimaprit, the H-2-agonist/H-3-antagonist, impromidine, the selective H-3-agonist, (R)alpha-methylhistamine ((R)alpha-MeHA) and the H-3-antagonist, thioperamide. 3 The H-1-agonists and the H-3-agonist (R)alpha-MeHA induced a concentration (100 nM-1 mM) and time-dependent release of PGI2 as determined by radioimmunoassay for 6-keto-PGF1alpha, but were less potent than histamine itself. The rank order of potency was the same following 30 min and 24 h incubation, i.e. histamine>ThEA>2-MeHA>>beta-His> (R)alpha-MeHA. 4 Histamine and 2-MeHA (1 muM - 1 mM), ThHEA (10 muM - 1 mM) and (R)alpha-MeHA (1 mM), but not beta-His, induced a significantly greater increase in PGI2 release after 24h incubation than after 30 min incubation (P < 0.05). 5 Neither the selective H-2-agonist, dimaprit, nor the H-2-agonist/H-3-antagonist, impromidine alone induced release of PGI2. 6 The H-1-antagonist, mepyramine (10 muM), abolished release of PGI2 induced by histamine, the H-1-agonists and (R)alpha-MeHA but the H-2-antagonist cimetidine (10 muM) and the H-2/H-3-antagonist, burimamide (10 muM) did not significantly modulate PGI2 release. 7 Although the H-3-agonist (R)alpha-MeHA induced release of PGI2, it failed to modulate PGI2 release in the presence of histamine. 8 Low concentrations of the H-3-antagonist, thioperamide (100 nM) did not modulate histamine release of PGI2 at all but after 24 h incubation, thioperamide (10(-4) M) partially reduced PGI2 release in the presence of histamine. 9 These results indicate that PGI2 from HUVEC is initiated and maintained via histamine H-1-receptor occupancy. There appears to be no involvement of either H-2- or H-3-receptors in this particular endothelial cell histaminergic response.