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.