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Stimulation of histamine H2- (and H1)-receptors activates Ca2+ influx in all-atrans-retinoic acid-differentiated HL-60 cells independently of phospholipase C or adenylyl cyclase

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Abstract

In human neutrophils, histamine H2-receptors mediate activation of adenylyl cyclase (AC) and inhibition of N-formyl-l-methionyl-l-leucyl-l-phenylalanine (FMLP)-induced superoxide anion (0 sup−inf2 ) formation, and in HL-60 promyelocytes, H2-receptors mediate parallel activation of AC, phospholipase C (PLC) and non-selective cation (NSC) channels. As all-trans-retinoic acid (RA) is successfully used in the differentiation therapy of acute promyelocytic leukaemia, we studied signal transduction in RA-differentiated HL-60 cells. Histamine and the H2-receptor agonist, impromidine, induced both rises in cAMP levels and cytosolic Ca2+ ([Ca2+]i). Substances acting at post-receptor sites to increase cAMP did not increase [Ca2+]i. H2-but not H1-receptor antagonists inhibited histamine-induced cAMP accumulation and rises in [Ca2+]i were more effectively inhibited by H2- than by H1-receptor antagonists. Histamine-induced rises in [Ca2+]i were completely dependent on the presence of extracellular Ca2+ and were abolished by the blocker of NSC channels, Gd3+, but were resistant to inhibition by pertussis toxin. Unlike FMLP, histamine did not activate PLC. The effects of FMLP on [Ca2+]i were less sensitive to blockade by Gd3+ than those of histamine, and there was no cross-desensitization between the two stimuli. FMLP, but not histamine, inhibited transiently thapsigargin-induced rises in [Ca2+]1. Taken together, our results show that histamine activates AC-mediated cAMP accumulation in RA-differentiated HL-60 cells via H2-receptors and NSC channel-mediated Ca2+ influx via H2- (and H1)-receptors. Histamine-induced NSC channel activation is not the consequence of AC- or PLC stimulation and occurs, directly or indirectly, via pertussis toxin-insensitive guanine nucleotide-binding proteins. FMLP and histamine activate Ca2+ influx by different mechanisms. There are similarities in H2-receptor-mediated signal transduction between RA-differentiated HL-60 cells and HL-60 promyelocytes and differences between the former cells and neutrophils, indicating that RA-differentiated HL-60 cells must be considered as partially immature.

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  1. Rahel Burde

    Present address: Medizinische Klinik und Poliklinik, Abteilung fur Innere Medizin mit Schwerpunkt Gastroenterologie, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, Hindenburgdamm 30, D-12200, Berlin, Germany

  2. Roland Seifert

    Present address: Department of Molecular and Cellular Physiology, B 157 Howard Hughes Medical Institute, Beckman Center for Molecular and Genetic Medicine, Stanford University Medical Center, 94305-5428, Stanford, CA, USA

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  1. Institut für Pharmakologie, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, Thielallee 69/73, D-14195, Berlin, Germany

    Rahel Burde & Roland Seifert

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Burde, R., Seifert, R. Stimulation of histamine H2- (and H1)-receptors activates Ca2+ influx in all-atrans-retinoic acid-differentiated HL-60 cells independently of phospholipase C or adenylyl cyclase. Naunyn-Schmiedeberg's Arch Pharmacol 353, 123–129 (1996). https://doi.org/10.1007/BF00168748

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  • DOI: https://doi.org/10.1007/BF00168748

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