David J. Taylor

Demonstration of histamine H2 receptors on human melanoma cells

Histamine induced a concentration-dependent increase in intracellular cyclic-AMP of the two human melanoma cell lines SK23 and DX3.LT5.1; maximal stimulation was obtained with 17.8 microM histamine which consistently produced greater than 50-fold increases in the cyclic AMP content of both cell lines. The dose-response curve for histamine in each culture was progressively displaced to the right with increasing concentrations of the histamine H2 receptor antagonist cimetidine. Ranitidine, another H2 receptor antagonist also prevented the histamine-induced cyclic AMP elevation, but the H1 receptor antagonists mepyramine and tripelennamine had no significant effect. These findings indicate that human melanoma cells express histamine H2 receptors, stimulation of which activates adenylate cyclase with a subsequent rise in intracellular cyclic AMP. Mast cell:melanoma interactions mediated by histamine in vivo might therefore be expected to modify some aspects of melanoma cell behaviour.

Comparative effects of interleukin 1 and a phorbol ester on rheumatoid synovial cell fructose 2,6-bisphosphate content and prostaglandin E production.

The addition of either recombinant human interleukin 1 (IL1 alpha) or 12-O-tetradecanoyl phorbol-13-acetate (TPA) to cultured rheumatoid synovial cells (RSC) caused dose-related increases in PGE production and cellular fructose 2,6-bisphosphate (Fru-2,6-P2). IL1 consistently produced the greater increases in both parameters. A close association between increases in PGE production and Fru-2,6-P2 was demonstrated for both IL1- and TPA-stimulated cells. The combined addition of IL1 with TPA resulted in an additive increase in both parameters. When IL1 was added together with human recombinant interferon-gamma (IFN-gamma), the resulting Fru-2,6-P2 level was synergistically increased, whilst the combination of IFN-gamma and TPA produced only an additive increase. Thus despite their very similar effects on RSC in culture, the data suggests that IL1 and TPA do not act via an identical intracellular mechanism.