Regulation of [Ca2+]i rise activated by doxepin-sensitive H1-histamine receptors in Jurkat cells, cloned human T lymphocytes.
To clarify the presence of histamine receptor and its transmembrane mechanism in human T lymphocytes, we investigated the effects of agonists or antagonists of histamine receptor subtypes and bacterial toxins on intracellular concentration of Ca2+ [Ca2+]i), [3H]pyrilamine binding and c-fos mRNA expression in Jurkat cells, cloned human T lymphocytes. H1-agonists (histamine and 2-methylhistamine) caused a transient rise of [Ca2+], and H1-antagonists (pyrilamine and doxepin) inhibited the histamine-induced [Ca2+]i rise more potently than the H2-antagonist (cimetidine) on the H3-antagonist (impromidine). Binding parameters of [3H]pyrilamine binding were Kd = 5.53 nM and Bmax = 2,647 sites/cell. Pretreatment with B.pertussis, V.cholera. or C.botulinum toxin did not influence histamine-induced [Ca2+]i rise. Western Blot analysis using antibodies against subunits of GTP-binding proteins indicated that Gq/G11 richly existed in Jurkat cells. Histamine induced mRNA expression of an immediate early gene c-fos. Pretreatment with a protein kinase C activator, phorbol 12-myristate 13-acetate, caused almost complete inhibition of histamine-induced [Ca2+]i rise, but did not do so by activators of cAMP- and cGMP-dependent protein kinases.
Kitamura
Y
Y
Department of Pharmacology, Hokkaido University, Sapporo, Japan.
Arima
T
T
Kitayama
Y
Y
Nomura
Y
Y
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004316:Doxepin / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis / Q000235:genetics; D011738:Pyrilamine / Q000378:metabolism; D051381:Rats; D011969:Receptors, Histamine H1 / Q000187:drug effects*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism*
D016760:Proto-Oncogene Proteins c-fos; D011969:Receptors, Histamine H1; D004316:Doxepin; D006632:Histamine; D019204:GTP-Binding Proteins; D011738:Pyrilamine; D002118:Calcium