Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.4.3 (phospholipase C)
18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The signalling pathway underlying histamine activation of non-selective cation channels was investigated in single equine tracheal myocytes. Application of histamine (100 microM) activated the transient calcium-activated chloride current (ICl(Ca)) and sustained, low amplitude non-selective cation current (ICat). The H1 receptor antagonist pyrilamine (10 microM) blocked activation of ICl(Ca) and ICat. Simultaneous application of histamine (100 microM) and caffeine (8 mM) during H1 receptor blockade activated ICl(Ca), but not ICat. Neither the H2 receptor antagonist cimetidine (20 microM) nor the H3 receptor antagonist thioperamide (20 microM) prevented activation of ICl(Ca) and ICat. 2. Intracellular dialysis of anti-Galphai/Galphao antibodies completely blocked activation of ICat by histamine, whereas ICl(Ca) was not affected. By contrast, anti-Galphaq/Galpha11 antibodies greatly inhibited ICl(Ca), but did not alter activation of ICat. 3. 1-Oleoyl-2-acetyl-sn-glycerol (OAG, 20-100 microM) did not induce any current or affect currents activated by histamine or methacholine (mACH). Simultaneous application of OAG and caffeine activated ICl(Ca), but not ICat, indicating that a rise in [Ca2+]i and stimulation of diacylglycerol-sensitive protein kinase C (PKC) is not sufficient to activate ICat. The phospholipase C inhibitor U73122 (2 microM) blocked histamine activation of ICl(Ca) and ICat, but simultaneous exposure of myocytes to histamine and caffeine restored both ICl(Ca) and ICat in the presence of U73122. 4. Histamine and mACH activated currents with equivalent I-V relationships. The currents activated by these agonists were not additive; following activation of ICat by mACH, histamine failed to induce an additional membrane current. Similarly, mACH did not induce an additional current after full activation of ICat by histamine. 5. We conclude that H1 histamine receptors activate ICat through coupling to Gi/Go proteins. Activation of ICat also requires intracellular calcium release, mediated by H1 receptors coupling to Gq/G11 proteins. This coupling is analogous to the activation of ICat by co-stimulation of M2 and M3 receptors.
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PMID:Signalling pathway for histamine activation of non-selective cation channels in equine tracheal myocytes. 1067 49

Histamine is a known secretagogue in adrenal chromaffin cells. Activation of G-protein linked H(1) receptors stimulates phospholipase C, which generates inositol trisphosphate leading to release of intracellular calcium stores and stimulation of calcium influx through store operated and other channels. This calcium leads to the release of catecholamines. In chromaffin cells, the main physiological trigger for catecholamine release is calcium influx through voltage-gated calcium channels (I(Ca)). Therefore, these channels are important targets for the regulation of secretion. In particular N- and P/Q-type I(Ca) are subject to inhibition by transmitter/hormone receptor activation of heterotrimeric G-proteins. However, the direct effect of histamine on I(Ca) in chromaffin cells is unknown. This paper reports that histamine inhibited I(Ca) in cultured bovine adrenal chromaffin cells and this response was blocked by the H(1) antagonist mepyramine. With high levels of calcium buffering in the patch pipette solution (10 mM EGTA), histamine slowed the activation kinetics and inhibited the amplitude of I(Ca). A conditioning prepulse to +100 mV reversed the kinetic slowing and partially relieved the inhibition. These features are characteristic of a membrane delimited, voltage-dependent pathway which is thought to involve direct binding of G-protein betagamma subunits to the Ca channels. However, unlike virtually every other example of this type of inhibition, the response to histamine was not blocked by pretreating the cells with pertussis toxin (PTX). The voltage-dependent, PTX insensitive inhibition produced by histamine was modest compared with the PTX sensitive inhibition produced by ATP (28% vs. 53%). When histamine and ATP were applied concomitantly there was no additivity of the inhibition beyond that produced by ATP alone (even though the agonists appear to activate distinct G-proteins) suggesting that the inhibition produced by ATP is maximal. When experiments were carried out under conditions of low levels of calcium buffering in the patch pipette solution (0.1 mM EGTA), histamine inhibited I(Ca) in some cells using an entirely voltage insensitive pathway. We demonstrate that activation of PTX insensitive G-proteins (most likely Gq) by H(1) receptors inhibits I(Ca). This may represent a mechanism by which histamine exerts inhibitory (in addition to previously identified stimulatory) effects on catecholamine release.
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PMID:Voltage-dependent, pertussis toxin insensitive inhibition of calcium currents by histamine in bovine adrenal chromaffin cells. 1071 70

Histamine-releasing neurons are located exclusively in the TM of the hypothalamus, from where they project to practically all brain regions, with ventral areas (hypothalamus, basal forebrain, amygdala) receiving a particularly strong innervation. The intrinsic electrophysiological properties of TM neurons (slow spontaneous firing, broad action potentials, deep after hyperpolarisations, etc.) are extremely similar to other aminergic neurons. Their firing rate varies across the sleep-wake cycle, being highest during waking and lowest during rapid-eye movement sleep. In contrast to other aminergic neurons somatodendritic autoreceptors (H3) do not activate an inwardly rectifying potassium channel but instead control firing by inhibiting voltage-dependent calcium channels. Histamine release is enhanced under extreme conditions such as dehydration or hypoglycemia or by a variety of stressors. Histamine activates four types of receptors. H1 receptors are mainly postsynaptically located and are coupled positively to phospholipase C. High densities are found especially in the hypothalamus and other limbic regions. Activation of these receptors causes large depolarisations via blockade of a leak potassium conductance, activation of a non-specific cation channel or activation of a sodium-calcium exchanger. H2 receptors are also mainly postsynaptically located and are coupled positively to adenylyl cyclase. High densities are found in hippocampus, amygdala and basal ganglia. Activation of these receptors also leads to mainly excitatory effects through blockade of calcium-dependent potassium channels and modulation of the hyperpolarisation-activated cation channel. H3 receptors are exclusively presynaptically located and are negatively coupled to adenylyl cyclase. High densities are found in the basal ganglia. These receptors mediated presynaptic inhibition of histamine release and the release of other neurotransmitters, most likely via inhibition of presynaptic calcium channels. Finally, histamine modulates the glutamate NMDA receptor via an action at the polyamine binding site. The central histamine system is involved in many central nervous system functions: arousal; anxiety; activation of the sympathetic nervous system; the stress-related release of hormones from the pituitary and of central aminergic neurotransmitters; antinociception; water retention and suppression of eating. A role for the neuronal histamine system as a danger response system is proposed.
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PMID:The physiology of brain histamine. 1116 99

The effect of histamine on intracellular free Ca2+ levels ([Ca2+]i) in HA22/VGH human hepatoma cells were evaluated using fura-2 as a fluorescent Ca2+ dye. Histamine (0.2-5 microM) increased [Ca2+]i in a concentration-dependent manner with an EC50 value of about 1 microM. The [Ca2+]i response comprised an initial rise, a slow decay, and a sustained phase. Extracellular Ca2+ removal inhibited 50% of the [Ca2+]i signal. In Ca2+-free medium, after cells were treated with 1 microM thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor), 5 microM histamine failed to increase [Ca2+]i. After pretreatment with 5 microM histamine in Ca2+-free medium for 4 min, addition of 3 mM Ca2+ induced a [Ca2+]i increase of a magnitude 7-fold greater than control. Histamine (5 microM)-induced intracellular Ca2+ release was abolished by inhibiting phospholipase C with 2 microM 1-(6-((17beta-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione (U73122), and by 5 microM pyrilamine but was not altered by 50 microM cimetidine. Together, this study shows that histamine induced [Ca2+]i increases in human hepatoma cells by stimulating H1, but not H2, histamine receptors. The [Ca2+]i signal was caused by Ca2+ release from thapsigargin-sensitive endoplasmic reticulum in an inositol 1,4,5-trisphosphate-dependent manner, accompanied by Ca2+ entry.
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PMID:Histamine-Induced increases in intracellular free Ca2+ levels in hepatoma cells. 1129 81

The effect of histamine on intracellular free Ca2+ levels ([Ca2+](i)) in MG63 human osteosarcoma cells was explored using fura-2 as a Ca2+ dye. Histamine increased ([Ca2+](i)) in a concentration-dependent fashion with an EC(50) value of 0.5 microM. Extracellular Ca2+ removal inhibited the ([Ca2+](i)) signals. Histamine failed to increase ([Ca2+](i)) in Ca2+-free medium after cells were pretreated with thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor). Addition of Ca2+ induced concentration-dependent ([Ca2+](i)) increases after preincubation with histamine in Ca2+-free medium. Histamine-induced intracellular Ca2+ release was abolished by inhibiting phospholipase C with 1-(6-((17beta-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione (U73122). The ([Ca2+](i)) increase induced by histamine in Ca2+ medium was abolished by cimetidine, but was not altered by pyrilamine, nifedipine, verapamil, and La(3+). Together, this study shows that histamine increased in ([Ca2+](i)) in osteosarcoma cells by stimulating H2 histamine receptors. The Ca2+ signal was caused by Ca2+ release from the endoplasmic reticulum in a phospholipase C-dependent manner. The Ca2+ release was accompanied by Ca(2+) influx.
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PMID:Mechanisms of histamine-induced intracellular Ca2+ release and extracellular Ca2+ entry in MG63 human osteosarcoma cells. 1137 83

The effect of histamine on intracellular free Ca2+ levels ([Ca2+]i) in PC3 human prostate cancer cells and the underlying mechanism were evaluated using fura-2 as a Ca2+ dye. Histamine at concentrations between 0.1 and 50 microM increased [Ca2+]i in a concentration-dependent manner with an EC50 value of 1 microM. The [Ca2+]i response comprised an initial rise and a slow decay, which returned to baseline within 3 min. Extracellular Ca2+ removal inhibited 50% of the [Ca2+]i signal. In the absence of extracellular Ca2+, after cells were treated with 1 microM thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor), 10 microM histamine did not increase [Ca2+]i. After pretreatment with 10 microM histamine in a Ca2+-free medium for several minutes, addition of 3 mM Ca2+ induced [Ca2+]i increases. Histamine (10 microM)-induced intracellular Ca2+ release was abolished by inhibiting phospholipase C with 2 microM 1-(6-((17 beta-3- methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione (U73122), and by 10 microM pyrilamine but was not altered by 50 microM cimetidine. Collectively, the present study shows that histamine induced [Ca2+]i transients in PC3 human prostate cancer cells by stimulating H1 histamine receptors leading to Ca2+ release from the endoplasmic reticulum in an inositol 1,4,5-trisphosphate-dependent manner, and by inducing Ca2+ entry.
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PMID:Mechanism underlying histamine-induced intracellular Ca2+ movement in PC3 human prostate cancer cells. 1173 64

Transient receptor potential (TRP) channels form a large family of plasma membrane cation channels. Mammalian members of the "short" TRP family (TRP channel (TRPC) 1-7 are Ca(2+)-permeant, non-selective cation channels that are widely expressed in various cell types, including neurons. TRPC activity is linked through unknown mechanisms to G-protein-coupled receptors or receptor tyrosine kinases that activate phospholipase C. To investigate the properties and function of TRPC4 in neuronally derived cells, we transiently expressed mouse TRPC4 and histamine H(1) receptor in mouse adrenal chromaffin cells and PC12 cells. Histamine, but not thapsigargin, stimulated Mn(2+) influx in transfected cells. In the whole-cell patch clamp mode, histamine triggered a transient current in TRPC4-expressing cells. No current was evoked by perfusion with inositol 1,4,5-trisphosphate. When exocytosis was monitored with the capacitance detection technique, the magnitude of the membrane capacitance increase (Delta C(m)) on application of histamine in H(1) receptor/TRPC4-expressing chromaffin cells was comparable with that triggered by a train of depolarizing pulses. Our results indicate that TRPC4 channels behave as receptor, but not store-operated, channels in neuronally derived cells. TRPC4 channels can provide sufficient Ca(2+) influx to trigger a robust secretory response in voltage-clamped neurosecretory cells. Similar mechanisms may modulate exocytosis in other neuronal systems.
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PMID:TRPC4 can be activated by G-protein-coupled receptors and provides sufficient Ca(2+) to trigger exocytosis in neuroendocrine cells. 1185 42

Histamine-evoked catecholamine secretion from bovine chromaffin cells was studied. Secretion was not prevented by inhibitors of IP3 receptors, protein kinase C, or phospholipase C; depleting Ca(2+) stores; or omitting extracellular Na(+) or Cl(-). Patch clamp studies showed histamine inhibited an M current, causing depolarization and firing of action potentials.
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PMID:How does histamine evoke catecholamine secretion from bovine chromaffin cells? 1243 7

Nerve growth factor induces innervation and epidermal hyperplasia in inflammatory skin diseases like psoriasis. Nerve growth factor production by keratinocytes is increased in the inflammatory lesions. Nerve growth factor induces histamine release from mast cells. We examined the in vitro effects of histamine on nerve growth factor production in human keratinocytes. Histamine enhanced nerve growth factor secretion, mRNA expression, and promoter activity in keratinocytes. Two TPA-response elements on the nerve growth factor promoter were responsible for the activation by histamine. Histamine enhanced transcriptional activity and DNA binding of activator protein 1 at the two TPA-response elements. It shifted the TPA-response-element-binding activator protein 1 composition from c-Jun homodimers to c-Fos/c-Jun heterodimers. Histamine transiently induced c-Fos mRNA expression, which was not detectable in unstimulated keratinocytes, whereas c-Jun mRNA expression was constitutive and was not altered by histamine. Histamine-induced enhancement of nerve growth factor secretion, promoter activity, activator protein 1 transcriptional activity, and c-Fos expression was suppressed by H1 antagonist pyrilamine, protein kinase C inhibitor calphostin C, and PD98059, an inhibitor of mitogen-activated protein kinase kinase 1. Histamine induced the translocation of protein kinase C activity from cytosol to membrane, which was suppressed by phospholipase C inhibitor U73122. It stimulated the phosphorylation of extracellular signal-regulated kinase, which was blocked by pyrilamine, calphostin C, and PD98059. These results suggest that histamine may enhance nerve growth factor production by inducing c-Fos expression in keratinocytes. These effects may be mediated by the H1-receptor-induced signaling cascade of phospholipase C-protein kinase C-mitogen-activated protein kinase kinase 1-extracellular signal-regulated kinase.
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PMID:Histamine enhances the production of nerve growth factor in human keratinocytes. 1292 17

Histamine produced concentration-dependent contractions in cat duodenal smooth muscle cells that were obtained by enzymatic digestion of smooth muscle with collagenase F. Pyrilamine, an H1 receptor antagonist, inhibited the contractile response while famotidine, an H2 receptor antagonist, augmented it. In cells with selectively preserved H1 receptors, produced by pretreatment with pyrilamine followed by inactivation of all unprotected receptors with N-ethylmaleimide, histamine-induced contraction was significantly augmented as compared with control cells. Pertussis toxin (PTX) had no effect on contraction, suggesting that the H1 receptor is coupled to a PTX-insensitive G protein. Gi2, Gi3, Go, Gs, and Gq subunits were present in cat duodenum, and histamine-induced contraction was inhibited by Gq antibody after cell permeabilization. Neomycin, a PLC inhibitor, inhibited the histamine-induced cell contraction, but not rhoCMB, a PLD inhibitor, or DEDA, a PLA2 inhibitor. Heparin, an IP3 receptor inhibitor, inhibited contraction whereas chelerythrine, a PKC inhibitor, had no effect. We conclude that histamine-induced contraction in cat duodenal smooth muscle cells is mediated by H1 receptors coupled to a PTX-insensitive Gq protein and results in activation of phosphatidylinositol-specific phospholipase C (PI-PLC).
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PMID:Signaling via histamine receptors in cat duodenal smooth muscle cells. 1465 Dec 59


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