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

---

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

Histamine, a ubiquitous cell-to-cell messenger, exerts its numerous actions through interaction with three pharmacologically distinct receptor subtypes, termed H1, H2 and H3. The design of selective agonists and antagonists has allowed to establish their respective pharmacological profile. Radioligand binding studies and, very recently, molecular biological studies have shown that they all belong to the superfamily of G-protein coupled receptors. H1 and H2-receptor antagonists have been successfully used for a long time in the treatment of allergy and ulcer, respectively. Some of them have been designed as highly potent and selective radioligands and have allowed to analyze the precise distribution of H1 and H2 receptors in various tissues including the brain. Recently, H1- and H2-receptor genes have been cloned in various animal species. Transfection of mammalian cells with these intronless genes has confirmed the respective coupling of H1 and H2 receptors with phospholipase C and adenylylcyclase. However, other known or unknown intracellular signals, could also be triggered by the stimulation in a transfected cell of a single H1 or H2 receptor through coupling to different G-proteins. A third histamine receptor subtype, the H3 receptor was evidenced in rodent and human brain by the inhibition of histamine release and synthesis it mediates in various areas. Thus, H3 receptors were considered as autoreceptors localized on histaminergic terminals. With the design of several potent and selective H3-receptor agonists and of an antagonist thioperamide, the critical role of H3 receptors in the control of histaminergic neurons in vivo was established.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Pharmacological properties of histamine receptor subtypes. 792 Jan 74

The effect of histamine on the phosphoinositide turnover and intracellular free calcium activity [Ca2+]i was examined in human glomerular epithelial cells in culture. Addition of histamine to glomerular epithelial cells resulted in formation of inositol phosphates in a time- and dose-dependent manner. A transient maximum of inositol trisphosphate (InsP3) was observed within 10 s. Stimulation of protein kinase C by short-term pretreatment (15 min) of glomerular epithelial cells with phorbol 12-myristate 13-acetate caused a dose-dependent inhibition of the histamine-induced inositol phosphate accumulation. The baseline of [Ca2+]i in the cells was 115 +/- 2.7 nmol/l (n = 103). Histamine (ED50: approx. 2 x 10(-7) mol/l) caused a rapid and transient increase in [Ca2+]i as detected by fura-2 microfluorimetry studies. In a calcium-free extracellular solution the rapid increase of [Ca2+]i was still present. The H1 receptor antagonist mepyramine (IC50: approx. 8 x 10(-9) mol/l) inhibited the histamine (10(-6) mol/l) response on [Ca2+]i. Cimetidine, a potent H2 receptor antagonist, showed no effect. This data indicates that H1 receptor activation causes hydrolysis of phosphatidylinositol 4, 5-bisphosphate by phospholipase C activation, and consecutive mobilization of intracellular calcium. Since histamine is a mediator of inflammation, antigen response and cellular injury, these findings could be of importance for the understanding of glomerular epithelial cell pathology.
...
PMID:Effects of histamine on inositol phosphates and intracellular Ca2+ in human glomerular epithelial cells. 797 Jan 17

To understand the contractile response to histamine, drug-induced tension developments were measured in intact and staphylococcal alpha-toxin-treated permeabilized smooth muscle preparations of rabbit lingual artery. Histamine produced an endothelium-independent contraction; the observed effect was antagonized by diphenhydramine and was attenuated by nifedipine. Histamine produced only transient contraction in the Ca(2+)-free bathing media. In permeabilized preparations, histamine-induced contraction was abolished by ryanodine (in the presence of caffeine) or prior repeated application of caffeine; however, contraction produced by IP3 was still observed under the same experimental condition as that of the histamine study. Histamine- or caffeine-induced contraction was abolished in the permeabilized preparations by prior repeated application of IP3; caffeine or IP3 produced contraction after repeated application of histamine. Ryanodine in the presence of histamine was ineffective on caffeine-induced contraction, suggesting that histamine by itself may not have the ability to act on caffeine-sensitive Ca2+ release channels. Neomycin and H-7 completely abolished the histamine-induced contraction. Hence, it is suggested that histamine can contract the lingual artery via H1-receptor-coupled phospholipase C activation, and the contraction consists of a phasic response evoked by Ca2+ release from the IP3- and caffeine-sensitive Ca2+ storage site and the tonic response generated by the voltage-dependent influx of Ca2+. It is also postulated that IP3 produced by histamine may be able to produce Ca2+ release from only a part of the intracellular Ca2+ stores in the smooth muscle of rabbit lingual artery.
...
PMID:[A mechanism underlying histamine-induced contraction in isolated rabbit lingual artery]. 817 80

1. The effect of histamine H1-receptor stimulation on inositol phospholipid hydrolysis has been investigated in the hamster vas deferens smooth muscle cell line, DDT1MF-2. 2. Histamine (EC50 = 27 microM) stimulated the accumulation of [3H]-inositol phosphates in DDT1MF-2 cells prelabelled with [3H]-myo-inositol. 2-Thiazolylethylamine (EC50 42 microM) produced a maximal response of similar magnitude to histamine while the maximal response obtained with N alpha-methylhistamine (EC50 = 72 microM) and 2-pyridylethylamine (EC50 = 85 microM) were much lower (circa 65%, histamine = 100%). 3. The H1-selective agonists 2-(3-fluorophenyl)-histamine (2-FPH) and 2-(3-chlorophenyl)-histamine (2-CPH) both appeared to act as partial H1-agonists in this system. Both compounds produced maximal responses of only 30% (with respect to histamine = 100) and were able to antagonize the inositol phosphate response to histamine (estimated Kp = 10.4 and 18.9 microM for 2-FPH and 2-CPH respectively). 4. The response to histamine was antagonized by the H1-antagonists, mepyramine (KD 0.4 nM), (+)-chlorpheniramine (KD 1.2 nM) and promethazine (KD 0.3 nM). Furthermore, the (-)-isomer of chlorpheniramine was approx. three orders of magnitude less potent than the corresponding (+)-isomer. 5. The response to histamine (0.1 mM) was not altered by prior treatment of cells with pertussis toxin (100 ng ml-1; 24 h) whereas the inositol phosphate response to adenosine A1-receptor stimulation in this cell line was significantly attenuated under these conditions. 6. These data indicate that histamine-stimulated inositol phospholipid hydrolysis in DDT1MF-2 cells is mediated via a classical H1-receptor. Furthermore, the results also suggest that histamine HI- and adenosine A,-receptors activate phospholipase C in DDTMF-2 cells via two different G-protein-coupled pathways.
...
PMID:Histamine H1-receptor-mediated inositol phospholipid hydrolysis in DDT1MF-2 cells: agonist and antagonist properties. 838 20

The aim of this study deals with the post-receptor events involved in the response of cultured smooth muscle (SMC) from human bronchi to various agonists of the contraction. [3H]inositol phosphates (IPs) were isolated by high performance liquid chromatography (HPLC) and intracellular Ca2+ concentration ([Ca2+]i) was determined with the Fura-2 fluorescence technique. Following 5 sec stimulation with histamine, an elevation of several [3H]IPs, in particular [3H]1,4-IP2, [3H]1,4,5-IP3 and [3H]1,3,4,5-IP4, above the control values was observed. Following an incubation of 10 or 15 sec with histamine, the content of [3H]1,4,5-IP3 declined towards its basal value, while the amount of metabolites ([3H]4-IP, [3H]1,4-IP2, [3H]1,3,4-IP3) increased with time; [3H]1,3,4,5-IP4 varied little between 5 and 10 sec and decreased at 15 sec. SMC responded also to carbachol and to prostaglandin F2 alpha (PGF2 alpha) by an enhanced production of [3H]IPs, whereas neurokinin A (NKA) had no effect on the turnover of [3H]IPs. Histamine, carbachol and PGF2 alpha evoked a transient elevation in [Ca2+]i, followed by a sustained increase. The duration of the transient elevation appeared similar to that of the increase in [3H]1,4,5-IP3. These results suggest that the 'phospholipase C-1,4,5-IP3-Ca2+ release' signalling pathway is involved in the physiological response of human airway SMC to histamine, carbachol and PGF2 alpha.
...
PMID:Signal transduction in smooth muscle cells from human airways. 846 52

GTP-binding proteins are known to play an important role in controlling mast-cell exocytosis and are described as the primary targets of peptidic mast-cell histamine releasers. The mechanism of inhibition of the mast-cell peptidergic pathway by alkylamines, which are selective inhibitors of this pathway, was investigated using intact or permeabilized rat peritoneal mast cells. Histamine release induced by GTP gamma S and by mastoparan (a venom peptide activating G proteins) was inhibited by pretreating mast cells with 0.1 to 3 micrograms/ml of a mixture of benzalkonium chloride containing in majority a twelve-carbon-atom aliphatic chain (BAC(C approximately 12)). Pure benzalkonium chloride, with a fourteen-carbon-atom aliphatic chain (BAC (C14)), at 5 to 10 microM also inhibited histamine release induced by GTP gamma S and mastoparan. The dose-response curve of mastoparan-induced histamine release from intact mast cells was shifted to the right by various concentrations of BAC (C14). Similar results were obtained with another alkylamine differing from BAC (C14) by the absence of the benzene ring, tetradecyltrimethylammonium bromide, TAB (C14). This illustrates that the presence of the phenyl radical is not required for the inhibitory effect of benzalkonium chloride. BAC (C approximately 12) and BAC (C14) inhibited the generation of inositol polyphosphates induced by GTP gamma S. BAC (C approximately 12) and TAB (C14) inhibited the mastoparan-stimulated GTPase activity from mast-cell Gi-like proteins. These results suggest that alkylamines exert selectively their inhibitory effect via an interaction with mast-cell Gi-like proteins coupled to phospholipase C, i.e., at an early stage in the stimulus-secretion coupling process.
...
PMID:The mechanism of inhibition of alkylamines on the mast-cell peptidergic pathway. 847 31

We have previously shown that myocardium from experimental autoimmune myocarditis expresses H1 receptors not present in normal mice heart. ThEA acting via H1 receptors, augments cyclic AMP production in atria from autoimmune myocarditis mice without any effect on atria from control mice. Addition of mepyramine before ThEA caused cyclic AMP levels to fall to a level similar to basal, confirming the H1 receptor participation. Histamine at low concentrations mimicked the ThEA action on H1 receptor-stimulation of cyclic AMP production by autoimmune myocardium. The fact that the inhibition of phospholipase C blocked the cyclic AMP stimulation by ThEA, supports the assumption that this action is secondary to receptor-mediated hydrolysis of phosphoinositides, generating some oxidative metabolites (IP3-DAG), which in turn may be responsible for the cyclic AMP effect. So, the inhibition of protein kinase C and calcium/calmodulin partially prevented the stimulatory action of ThEA on cyclic AMP levels in autoimmune myocardium, suggesting that both pathways are implicated in this effect. Data shows that the stimulation of H1 receptors by specific agonist in atria from autoimmune myocarditis mice, augments the cyclic AMP, requiring the hydrolysis of phosphoinositide cycle. The role of this cyclic AMP augmentation in myocardium from autoimmune myocarditis mice, will provide a basis to assess the role of this second messenger as an important factor in the regulation and/or modulation of the physiological behaviour of the heart in the course of autoimmune myocarditis.
...
PMID:Increases in cyclic AMP levels couple to H1 receptors in atria from autoimmune myocarditis mice. 859 44

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 (O2-) 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+]. 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.
...
PMID:Stimulation of histamine H2- (and H1)-receptors activates Ca2+ influx in all-trans-retinoic acid-differentiated HL-60 cells independently of phospholipase C or adenylyl cyclase. 871 51

1. HL-60 human leukemia cells are a widely employed model system for the analysis of signal transduction processes mediated via regulatory heterotrimeric guanine nucleotide-binding proteins (G-proteins). HL-60 promyelocytes are pluripotent and can be differentiated into neutrophilic or monocytic cells. 2. HL-60 cells express formyl peptide-, complement C5a-, leukotriene B4 (LTB4)- and platelet-activating factor receptors, receptors for purine and pyrimidine nucleotides, histamine H1- and H2-receptors, beta 2-adrenoceptors and prostaglandin receptors. 3. The major G-proteins in HL-60 cells are pertussis toxin (PTX)-sensitive Gi-proteins (Gi2 > Gi3). Gs-proteins and G-proteins of the Gq-family (e.g., G16) are expressed, too. 4. G-protein-regulated effector systems in HL-60 cells are adenylyl cyclase and phospholipase C-beta 2 (PLC-beta 2) and, possibly, phospholipase D (PLD), nonselective cation (NSC) channels and NADPH oxidase. 5. The expression of signal transduction pathways in HL-60 cells strongly depends on the differentiation state of cells. 6. Formyl peptides, via Gi-proteins, mediate activation of PLC, PLD, NSC channels, NADPH oxidase and azurophilic granule release and are referred to as full secretagogues. In dibutyryl cAMP (Bt2cAMP)-differentiated HL-60 cells, C5a and LTB4 are partial and incomplete secretagogues, respectively. There are substantial differences in the Gi-protein activations induced by formyl peptides, C5a and LTB4. 7. In HL-60 promyelocytes, purine and pyrimidine nucleotides mediate activation of PLC and NSC channels largely via PTX-insensitive G-proteins and induce functional differentiation. In Bt2cAMP-differentiated HL-60 cells, they additionally activate PLD, NADPH oxidase and granule release via PTX-sensitive and -insensitive pathways. ATP and UTP are partial secretagogues. Multiple types of receptors (i.e., P2Y- and P2U-receptors and pyrimidinocyeptors) may mediate the effects of nucleotides in HL-60 cells. 8. Bt2cAMP- and 1 alpha,25-dihydroxycholecalciferol-differentiated HL-60 cells express H1-receptors coupled to Gi-proteins and PTX-insensitive G-proteins. In the former cells, histamine mediates activation of PLC and NSC channels, and in the latter, activation of NSC channels. Histamine is an incomplete secretagogue in these cells. 9. HL-60 promyelocytes express H2-receptors coupled to adenylyl cyclase, PLC, and NSC channels. There are substantial differences in the agonist/antagonist profiles of H2-receptor-mediated cAMP formation and rises in cytosolic Ca2+ concentration, indicative of the involvement of different H2-receptor subtypes. H2-receptors mediate functional differentiation of HL-60 cells. 10. Certain cationic-amphiphilic histamine receptor ligands (i.e., 2-substituted histamines, lipophilic guanidines, and a histamine trifluoromethyl-toluidide derivative) show stimulatory effects in HL-60 cells that are attributable to receptor-independent activation of Gi-proteins.
...
PMID:G-protein-coupled receptors in HL-60 human leukemia cells. 874 93

Hyperreactive responses of asthmatics to bronchoconstrictor agonists are caused by mediators produced by a variety of cell types within the airways. Nerves, mast cells, eosinophils, airway epithelia and airway smooth muscle cells probably all interact to increase bronchomotor tone in response to challenge with allergenic stimuli. In addition to important cell-cell interactions, there may be a significant postjunctional component of airway hyperreactivity in which mediators interact at the level of airway smooth muscle cells. To test this hypothesis, I investigated synergistic interactions of methacholine (MCH), histamine and serotonin using intact and chemically skinned canine tracheal smooth muscle. A threshold concentration of histamine (100 nM) significantly increased force when it was added 20 min after or 10 min before stimulation with low concentrations of MCH (1-10 nM). A threshold concentration of serotonin (10 nM) also significantly increased contractions induced by MCH. Serotonin (10 nM) added during a steady-state contraction induced by 6 or 10 nM MCH increased force and increased fura-2 fluorescence, which suggests that force increases in part because myoplasmic Ca++ increases. I also tested the hypothesis that mechanisms beyond the initial steps of signal transduction contribute to synergism by permeabilizing tracheal smooth muscle fibers with staphylococcal alpha-toxin. Histamine (30 microM), MCH (1 microM), GTP-gamma-S (100 microM) and phorbol dibutyrate (1 microM) all potentiated contractions induced by 1 microM Ca++ in skinned fibers. These data suggest that postjunctional components of airway hyperreactivity may be a combination of synergistic effects of agonists occurring at the level of excitation-contraction coupling as well as sensitization of contractile proteins to Ca++.
...
PMID:Agonist synergism in airway smooth muscle contraction. 876 34


<< Previous 1 2 3 4 5 6 7 8 Next >>

---