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Agonistic activities of histamine-albumin conjugates at histamine H2 receptors on human HL-60 promyelocytic leukemia cells

M Mitsuhashi, T Mitsuhashi, PF Dazin and DG Payan

Howard Hughes Medical Institute Laboratory, San Francisco, California.

We previously identified functional histamine H2 receptors on human HL- 60 promyelocytic leukemia cells [J. Biol. Chem. 264: 18356-18362 (1989)]. In the present study, we have compared the action of histamine- albumin conjugates on H2 receptor activation with that of histamine alone. Both histamine and conjugates increased intracellular levels of Ca2+ in an H2 receptor-specific manner. However, binding of fluoresceinated histamine-albumin conjugates to HL-60 cells was not dissociated by 10(-4) M unlabeled histamine, although this concentration of histamine significantly desensitized conjugate responses. These data suggest that histamine-albumin conjugates not only activate H2 receptors but also bind to HL-60 cells nonspecifically or in an H2 receptor-unrelated manner. Moreover, histamine-induced Ca2+ mobilization was transient, whereas conjugate-induced Ca2+ mobilization was sustained for more than 10 min, as a result of the influx of extracellular Ca2+. Therefore, the functional difference between histamine and conjugates may provide a good model for the further understanding of the activation mechanisms of receptor-operated Ca2+ influx.

Volume 40, Issue 2, pp. 271-275, 08/01/1991
Copyright © 1991 by American Society for Pharmacology and Experimental Therapeutics






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Copyright © 1991 by the American Society for Pharmacology and Experimental Therapeutics