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Characterization of histamine receptor sub‐types regulating prostacyclin release from human endothelial cells
Author(s) -
Bull Helen A.,
Courtney P.F.,
Rustin M.H.A.,
Dowd Pauline M.
Publication year - 1992
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1992.tb12738.x
Subject(s) - dimaprit , thioperamide , histamine , agonist , mepyramine , histamine h2 receptor , medicine , endocrinology , chemistry , histamine h3 receptor , prostacyclin , prostaglandin d2 , antagonist , biology , prostaglandin , receptor , biochemistry
1 The histamine receptor sub‐types that are involved in the initiation and maintenance of prostacyclin (PGI 2 ) 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, β‐histine (β‐His), the selective H 2 ‐agonist, dimaprit, the H 2 ‐agonist/H 3 ‐antagonist, impromidine, the selective H 3 ‐agonist, ( R )α‐methylhistamine (( R )α‐MeHA) and the H 3 ‐antagonist, thioperamide. 3 The H 1 ‐agonists and the H 3 ‐agonist ( R )α‐MeHA induced a concentration (100 n m ‐1 m m ) and time‐dependent release of PGI 2 as determined by radioimmunoassay for 6‐keto‐PGF 1α , 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 ≫ β‐His > ( R )α‐MeHA. 4 Histamine and 2‐MeHA (1 μ m ‐1 m m ), ThHEA (10 μ m ‐1m m ) and ( R )α‐MeHA (1 m m ), but not β‐His, induced a significantly greater increase in PGI 2 release after 24 h 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 PGI 2 . 6 The H 1 ‐antagonist, mepyramine (10 μ m ), abolished release of PGI 2 induced by histamine, the H 1 ‐agonists and ( R )α‐MeHA but the H 2 ‐antagonist cimetidine (10 μ m ) and the H 2 /H 3 ‐antagonist, burimamide (10 μ m ) did not significantly modulate PGI 2 release. 7 Although the H 3 ‐agonist ( R )α‐MeHA induced release of PGI 2 , it failed to modulate PGI 2 release in the presence of histamine. 8 Low concentrations of the H 3 ‐antagonist, thioperamide (100 n m ) did not modulate histamine release of PGI 2 at all but after 24 h incubation, thioperamide (10 −4 m ) partially reduced PGI 2 release in the presence of histamine. 9 These results indicate that PGI 2 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.