Mouse P19 Embryonal Carcinoma Cells Express Functional Histamine H1-Receptors

Bloemers, S. Margreet; Leurs, Rob; Smit, Martine J.; Verheule, Sander; Tertoolen, Leon G.J.; Timmerman, H.; Laat, Siegfried W. de

doi:10.1006/bbrc.1993.1192

Cited by 15 publications

(16 citation statements)

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“…The possible effects of the H1R knock-out on other developing monoaminergic neurotransmitter systems or on other histamine receptors have not yet been studied in these animals. Bloemers et al (1993) have demonstrated in vitro H1R-mediated signal transduction in P19 embryonal carcinoma (EC) cells, which are often used as a model to study differentiation in the early mouse embryo because of their similarity with the inner cell mass cells of the blastocyst stage (Martin, 1980). However, it remains to be studied whether functional H1-receptors exist in vivo, or at later embryonal stages.…”

Section: Discussionmentioning

confidence: 99%

In situ detection of H1-receptor mRNA and absence of apoptosis in the transient histamine system of the embryonic rat brain

et al. 1998

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In the developing brain, histamine is one of the first neurotransmitters to appear. The concentration of histamine in the prenatal brain is fivefold that of adult levels. During the prenatal development a large transiently histamine-immunoreactive cell population distinct from the adult histaminergic system can be found within a subpopulation of the developing serotonergic raphe nuclei neurons. Also histamine-immunoreactive nerve fibers are widely distributed already during the prenatal development extending to the diencephalon, the thalamus, the cortex, and the spinal cord. Large numbers of histamine-containing mast cells also migrate into the brain during the late prenatal life. The wide distribution and high prenatal concentrations imply important functions for the histaminergic system during intrauterine development. However, little is known about the actual functions of histamine during development, and which of the histamine receptors are present in the prenatal rat brain is currently unknown. In the present study, we used in situ hybridization to study the distribution of H1-receptor (H1R) mRNA in the embryonic rat brain and spinal cord. H1R mRNA could be detected in rat brain and in spinal cord on embryonic day (E) 14, and the expression pattern seemed to partially localize in areas containing histamine-immunoreactive nerve fibers through E14-E20. H1R mRNA was also detected by reverse transcriptase polymerase chain reaction from embryonic brain samples and by Northern hybridization. The possible involvement of apoptosis in the disappearance of the developing transiently histaminergic system was studied by using apoptosis detection based on the terminal dUTP nick end labeling (TUNEL) technique and with c-Fos immunostaining. Although histamine immunoreactivity disappears dramatically from the developing raphe nuclei after E18, only occasional apoptotic nuclei could be seen in the histamine-immunoreactive cell bodies. The presence of H1R mRNA during the embryonic development renders it possible that histamine could exert an H1R-specific function at the time of the embryonic histamine peak.

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Section: Discussionmentioning

confidence: 99%

In situ detection of H1-receptor mRNA and absence of apoptosis in the transient histamine system of the embryonic rat brain

et al. 1998

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“…[ 3 H]Pyrilamine Binding-Scatchard analysis on membrane preparations and intact cells was performed as described earlier (16). For Scatchard analysis, cells were serum-starved for 1 h, after which they were labeled for 1 h at 4°C in Hepes-buffered Dulbecco's modified Eagle's medium containing 4 nM [ 3 H]pyrilamine and different concentrations of unlabeled pyrilamine, after which total binding reached plateau phase (not shown).…”

Section: Methodsmentioning

confidence: 99%

“…We have reported earlier that the P19 embryo carcinoma (EC) 1 cell, a pluripotent cell type resembling the inner cell mass of the embryo, expresses functional histamine H 1 receptors (16), although its function with respect to embryogenesis is not clear. To obtain more insight into the function of histamine receptor expression in uncommitted cells, we decided to investigate the presence of cellular responses to histamine in other pluripotent cells.…”

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confidence: 99%

Sensitization of the Histamine H1 Receptor by Increased Ligand Affinity

Bloemers¹,

Verheule²,

Peppelenbosch³

et al. 1998

Journal of Biological Chemistry

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Histamine regulates a variety of physiological processes including inflammation, gastric acid secretion, and neurotransmission. The cellular response to histamine is subject to dynamic control, and exaggerated histamine reactivity in response to cysteinyl leukotrienes and other stimuli is important in a variety of different pathological conditions. The molecular mechanisms controlling histamine responsiveness are still unresolved. In investigating histamine responses in embryonic stem (ES5) and F9 embryonic carcinoma cells, we encountered a novel mechanism controlling the cellular reaction to histamine. Unstimulated cells displayed neither [ 3 H]pyrilamine binding nor histamineinduced increases in cytosolic Ca 2؉ levels. Pretreatment of these cells, however, with leukotriene D 4 , leukotriene E 4 , serotonin, or fetal calf serum induced an immediate and transient ability of these cells to respond to histamine with an increase in cytosolic Ca 2؉ levels. This effect could be inhibited by pertussis toxin and was mimicked by GTP analogues. Importantly, the latter compounds also provoked immediate high affinity [ 3 H]pyrilamine binding. We conclude that in these cells histamine responsiveness is directly controlled by pertussis toxin-sensitive G protein-coupled receptors, whose activation enables the H 1 receptor to bind its ligand. These findings define a novel mechanism for regulating histamine H 1 receptor activity and provide for the first time molecular insight into the mechanism by which cysteinyl leukotrienes and other external stimuli can increase histamine responsiveness.

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“…Other authors reported histamine formation in mouse preimplantation embryos [1] and functional H 1 R-expression in the ES cell related mouse P19 embryonal carcinoma cells [5].…”

Section: Resultsmentioning

confidence: 99%