Histamine and calcium are independently regulated intracellular mediators of lymphocyte mitogenesis

• Published in: Biochemical and biophysical research communications Vol. 182; no. 2; pp. 786 - 793
• Main Authors: Brandes, Lorne J., LaBella, Frank S.
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 31.01.1992; Elsevier
• Subjects: Animals; Biological and medical sciences; Calcium - metabolism; Calcium Channels; Cell Membrane - metabolism; Cells, Cultured; Cerebral Cortex - metabolism; Cimetidine - pharmacology; Concanavalin A - pharmacology; DNA Replication - drug effects; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Histamine - biosynthesis; Histamine - metabolism; Histamine Antagonists - pharmacology; Immunobiology; Kinetics; Lymphocytes - drug effects; Lymphocytes - immunology; Lymphocytes - physiology; Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation; Mice; Mice, Inbred BALB C; Phenyl Ethers - pharmacology; Pyrilamine - pharmacology; Rats; Receptors, Histamine H1 - drug effects; Receptors, Histamine H1 - metabolism; Receptors, Nicotinic - metabolism; Spleen - physiology; Verapamil - metabolism; Verapamil - pharmacology; Cell proliferation; Spleen; Cell culture; Radiolabelling; Rodentia; DNA synthesis; Calcium Ions; Histamine; Vertebrata; Mammalia; Mouse; Biogenic amine; Mitogen; Lymphocyte
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/0006-291X(92)91801-V

In addition to cytosolic calcium ([Ca 2+] i), intracellular histamine has been implicated as a mediator of mitogenesis in normal mouse spleen cells stimulated by the plant lectin, concanavalin (Con) A. We have linked the growth-promoting action of this amine with its binding to distinct intracellular sites, designated H IC, in microsomes and nuclei and shown that the proliferative response of lymphocytes can be blocked by antagonizing the binding of histamine to H IC by N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine. HCl (DPPE), or by depleting intracellular histamine levels by the specific irreversible inhibitor of histidine decarboxylase, α-FMH. We now demonstrate that, at a concentration which completely inhibits both 3H-histamine binding to H IC and 3H-thymidine incorporation into DNA, DPPE fails to block the acute (30 seconds) rise in [Ca 2+] i in spleen cells exposed to Con A. Conversely, the calcium channel antagonist, verapamil, suppresses the Con A-induced rise in [Ca 2+] i at a concentration which correlates with its inhibition of thymidine incorporation into DNA, but does not prevent histamine synthesis or bind to H IC. Thus, in Con A-stimulated lymphocytes, intracellular histamine and calcium appear to be independently regulated, but essential, mediators of the proliferative response.