Differential Effects of Histamine Receptor Antagonists on Human Natural Killer Cell Activity

Hellstrand, Kristoffer; Hermodsson, Svante

doi:10.1159/000234431

Cited by 17 publications

(14 citation statements)

References 16 publications

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“…These channels are required for a variety of effector functions, including mitogenesis, secretion of lymphokines (27), cytolysis of target cells by natural killer cells (28) and volume regulation (29), and their expression follows T-cell differentiation (23). On the other hand, recent data indicate that 5-HT acts directly through various receptors on the cellular components of the immune system: this biogenic amine increases chemotactic activity of human lymphocytes (30), suppresses mitogeninduced proliferation of murine lymphocytes (31), modulates interferon y-induced macrophage phagocytosis (10), and increases the cytotoxicity of natural killer cells (9). It is therefore attractive to suggest that, as in neurons, 5-HT acts on the immune cells by, at least in part, regulating ionic permeabilities.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, the activation kinetics display a more complex behavior [such is also the case in T cells (17)] and was thus not extensively studied here because in first approximation it changed in parallel with inactivation upon different regulatory stimuli, such as increase ofinternal Ca2', cAMP (14), or 5-HT. Because leakage currents are small in these cells (input resistance, [1][2][3][4][5][6][7][8][9][10] Gfk), the amplitude of the potassium current could be measured in this study between base line and peak current. Potassium currents were generally elicited by depolarizing voltage steps of 80 mV (jumping from a holding potential of -80 mV) in order to (i) avoid contamination by unspecific leakage currents (for which the electrical driving force is null at 0 mV) and (ii) because the K+ conductance and inactivation rates are close to maximum at this null potential (see also Fig.…”

Section: Methods Electrophysiological Recordings Patch-clamp Experimmentioning

confidence: 99%

“…Serotonin, a major neurotransmitter (see, for example, refs. 2-4), has also been reported to modulate various aspects of the immune response (5)(6)(7)(8)(9)(10), although the specific molecular targets that mediate these effects are unidentified. In the nervous system, this transmitter operates, at least in part, by modulating potassium conductances (2,(11)(12)(13).…”

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confidence: 99%

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Dual effects of serotonin on a voltage-gated conductance in lymphocytes.

Choquet

Korn²

1988

Proc. Natl. Acad. Sci. U.S.A.

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The effects of serotonin (5-HT), a well-known immunomodulator and neurotransmitter, on the ionic permeability of a pre-B lymphocyte cell line was investigated with the whole-cell patch-clamp technique. We found that physiological doses of this biogenic amine regulate a voltage-gated potassium channel by activating different subsets of receptors. More specifically, 5-HT induces in the recorded cells (a) increase in the maximum potassium conductance, which is due to activation of 5-HT,-like receptors, and (ii) acceleration of the inactivation process that is under the control of 5-HT3 receptors and, accordingly, is mimicked by the 5-UT3 agonist, 2-methyl-5-HT; involvement of those two distinct categories of receptors was demonstrated by using specific antagonists that block predominantly one or the other of these two actions. These two results show that hormones can affect lymphocyte physiology through modulation of their ionic conductances in a way that might help explain some of the diverse effects of 5-HT on neuronal cells.Lymphocytes have receptors for a variety of hormones (for review, see ref. 1). Serotonin, a major neurotransmitter (see, for example, refs. 2-4), has also been reported to modulate various aspects of the immune response (5-10), although the specific molecular targets that mediate these effects are unidentified. In the nervous system, this transmitter operates, at least in part, by modulating potassium conductances (2,(11)(12)(13). Because a voltage-gated potassium channel is present in B lymphocytes (14), as in other cells ofthe immune system (15, 16), we investigated whether serotonin also modulates these channels in a pre-B cell line, found such to be the case, and further found that this amine acts on the activation and inactivation processes through distinct categories of receptors. This finding indicates common features for the effects of transmitters on the central nervous system and on the immune system. METHODS Electrophysiological Recordings. Patch-clamp experimentswere done on the Abelson murine leukemia virus-infected 18-81 pre-B cell line (for details see ref. 14). Just before recording (at room temperature 22-240C), the cells were washed of culture medium and bathed in 150 mM NaCl/4 mM KCl/1 mM MgCl2/1 mM CaCl2/10 mM Hepes buffer, pH 7.2.The pipette solution was 140 mM KCl/4 mM NaCl/4 mM MgCl2/0.55 mM CaCl2/1.1 mM EGTA, pCa 7, 5 mM creatine phosphate/2.5 mM ATP/0.2 mM GTP/10 mM Hepes buffer, pH 7.2. Compounds for these, and for serotonin 5-hydroxytryptamine (5-HT) (creatine sulfate complex) solutions were from Sigma. Stocks of 20 mM 5-HT were dissolved in Ringer's solution at the desired concentration just before use and applied through a slow perfusion system placed near the recorded cell (1-2 ml/min; dead volume, 400 IA).Current Parameter Measurements. The decaying part ofthe current is well-fitted by a single exponential function, and this property allows a simple estimate of the inactivation rates. In contrast, the activation kinetics display a more complex behavior [...

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Section: Discussionmentioning

confidence: 99%

Section: Methods Electrophysiological Recordings Patch-clamp Experimmentioning

confidence: 99%

mentioning

confidence: 99%

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Dual effects of serotonin on a voltage-gated conductance in lymphocytes.

Choquet

Korn²

1988

Proc. Natl. Acad. Sci. U.S.A.

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“…In itro, addition of exogenous 5-HT has been found to suppress phytohaemagglutinin (PHA)-induced blastogenesis [5]. 5-HT has been found to augment interferon-γ-induced phagocytosis [6] and natural killer cytotoxicity of human CD16 + \non-T-lymphocytes [7]. Recently there has been an upsurge of information indicating that 5-HT can stimulate the immune system via lymphocyte membrane receptors [3,[8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Ionotrophic 5-hydroxytryptamine type 3 receptor activates the protein kinase C-dependent phospholipase D pathway in human T-cells

Khan

Hichami

1999

Biochemical Journal

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The present study was undertaken to investigate the role of the 5-hydroxytryptamine (5-HT) ionotrophic receptor 5-HT3 in the activation of human Jurkat T-cells. 5-HT and 2-methyl-5-HT (2Me-5-HT), an agonist of the 5-HT3 receptor, induced increases in intracellular free Na+ concentrations, [Na+]i, via opening of the ionotrophic receptor in these cells. These two serotonergic (5-hydroxytryptaminergic) agents potentiated phytohaemagglutinin (PHA)-induced T-cell activation. However, they failed to potentiate dioctanoglycerol-plus-ionomycin-stimulated T-cell blastogenesis. Interestingly, an inhibitor of protein kinase C (PKC), GF 109203X, curtailed significantly 5-HT and 2Me-5-HT-potentiated T-cell activation. These results demonstrate that the opening of the 5-HT3 ionotrophic receptor is implicated in T-cell activation via the PKC pathway. Furthermore, 5-HT and 2Me-5-HT stimulated phospholipase D (PLD) activity, as measured by the production of phosphatidylethanol and phosphatidylbutanol at the expense of phosphatidic acid (PA). GF 109203X significantly curtailed the 5-HT- and 2Me-5-HT-induced PLD activity and T-cell activation. The PLD/PA pathway stimulated by these two serotonergic agents resulted in the production of 1,2-diacylglycerol (DAG) mass in Jurkat T-cells. These results altogether suggest that 5-HT and 2Me-5-HT potentiate T-cell activation via increases in [Na+]i and the activation of the PKC-dependent PLD pathway.

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“…Similarly, addition of exogenous 5-HT in itro was found to suppress phytohaemagglutinin-induced blastogenesis [7]. 5-HT has also been shown to augment interferon-γ-induced phagocytosis [8] and natural killer cell cytotoxicity [9]. Besides, pharmacological data have suggested a multiplicity of 5-HT receptors at the lymphocyte level [3][4][5], and molecular biology data have confirmed unequivocally the existence of multiple serotonergic receptors [10].…”

Section: Introductionmentioning

confidence: 99%

5-Hydroxytryptamine-induced calcium-channel gating in rainbow trout (Oncorhynchus mykiss) peripheral blood lymphocytes

Ferrière

Khan

Meyniel

et al. 1997

Biochemical Journal

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The present study was conducted on peripheral blood lympho-cytes of rainbow trout (Oncorhynchus mykiss) to assess the role of 5-hydroxytryptamine (5-HT; ‘serotonin’) in calcium signalling. 5-HT-induced increases in intracellular free calcium concentrations, [Ca2+]i, and its action was mediated by 5-HT receptor subtype 3 (5-HT3), but not by 5-HT receptor subtype 1A (5-HT1A) or subtype 2 (5-HT2) in these cells. In Ca2+-containing medium (1 mM CaCl2), 5-HT and 2-methyl-5-HT (5-HT3 receptor agonist) induced increases in [Ca2+]i, whereas in Ca2+-free medium (0 Ca2+, 1 mM EGTA), these two agents failed to evoke increases in [Ca2+]i in these cells, demonstrating that 5-HT mobilizes Ca2+ from the extracellular environment. Furthermore, 5-HT-induced increases in [Ca2+]i are not contributed to by the intracellular endoplasmic reticulum (ER) pool, as thapsigargin, an agent that recruits Ca2+ from ER stores, had additive effects on 5-HT-induced [Ca2+]i responses in fish peripheral lymphocytes. 5-HT-induced increases in [Ca2+]i were mediated by 5-HT3 receptors via gating the calcium through L-type, but not N-type, calcium channels in trout lymphocytes.

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Differential Effects of Histamine Receptor Antagonists on Human Natural Killer Cell Activity

Cited by 17 publications

References 16 publications

Dual effects of serotonin on a voltage-gated conductance in lymphocytes.

Dual effects of serotonin on a voltage-gated conductance in lymphocytes.

Ionotrophic 5-hydroxytryptamine type 3 receptor activates the protein kinase C-dependent phospholipase D pathway in human T-cells

5-Hydroxytryptamine-induced calcium-channel gating in rainbow trout (Oncorhynchus mykiss) peripheral blood lymphocytes

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