Characterization of histamine receptor sub-types 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 H1-receptor agonists, 2-methyl histamine (2-MeHA) or thiazolylethylamine (ThEA), the H1-agonist/H3-antagonist, beta-histidine (beta-His), the selective H2-agonist, dimaprit, the H2-agonist/H3-antagonist, impromidine, the selective H3-agonist, (R)alpha-methylhistamine ((R)alpha-MeHA) and the H3-antagonist, thioperamide. 3. The H1-agonists and the H3-agonist (R)alpha-MeHA induced a concentration (100 nM-1 mM) and time-dependent release of PGI2 as determined by radioimmunoassay for 6-keto-PGF1 alpha, 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 microM-1 mM), ThHEA (10 microM-1 mM) and (R)alpha-MeHA (1 mM), but not beta-His, induced a significantly greater increase in PGI2 release after 24 h incubation than after 30 min incubation (P < 0.05). 5. Neither the selective H2-agonist, dimaprit, nor the H2-agonist/H3-antagonist, impromidine alone induced release of PGI2. 6. The H1-antagonist, mepyramine (10 microM), abolished release of PGI2 induced by histamine, the H1-agonists and (R)alpha-MeHA but the H2-antagonist cimetidine (10 microM) and the H2/H3-antagonist, burimamide (10 microM) did not significantly modulate PGI2 release. 7. Although the H3-agonist (R)alphax-MeHA induced release of PGI2, it failed to modulate PGI2 release in the presence of histamine.8. Low concentrations of the H3-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 HI-receptor occupancy. There appears to be no involvement of either H2- or H3-receptors in this particular endothelial cell histaminergic response.
Bull
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HA
Department of Dermatology, University College and Middlesex School of Medicine, London.
Courtney
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Rustin
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Dowd
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PM
D002478:Cells, Cultured; D017259:Dimaprit / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011464:Epoprostenol / Q000378:metabolism*; D006632:Histamine / Q000494:pharmacology; D017442:Histamine Agonists / Q000494:pharmacology; D006801:Humans; D017446:Impromidine / Q000494:pharmacology; D008761:Methylhistamines / Q000494:pharmacology; D011968:Receptors, Histamine / Q000502:physiology*; D011969:Receptors, Histamine H1 / Q000502:physiology; D011970:Receptors, Histamine H2 / Q000502:physiology; D018100:Receptors, Histamine H3; D013844:Thiazoles / Q000494:pharmacology; D014471:Umbilical Veins
D017442:Histamine Agonists; D008761:Methylhistamines; D011968:Receptors, Histamine; D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; D018100:Receptors, Histamine H3; D013844:Thiazoles; C029345:2-(2-aminoethyl)thiazole; C069357:alpha-methylhistamine; D006632:Histamine; D017446:Impromidine; D011464:Epoprostenol; C026259:2-methylhistamine; D017259:Dimaprit