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Manfred Göthert - One of the best experts on this subject based on the ideXlab platform.
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N-methyl-d-aspartate (NMDA)-stimulated noradrenaline (NA) release in rat brain cortex is modulated by presynaptic H_3-receptors
Naunyn-Schmiedeberg's Archives of Pharmacology, 1994Co-Authors: K. Fink, Eberhard Schlicker, Manfred GöthertAbstract:In superfused rat brain cortex slices and synaptosomes preincubated with [^3H]noradrenaline the effect of agonists or antagonists at presynaptic H_3 receptors on NMDA-evoked [^3H]noradrenaline release was investigated. In experiments on slices , histamine and the preferential H_3 receptor agonist R-(−)-α-methylhistamine inhibited NMDA-evoked tritium overflow (IC_20 values 0.27 μmol/l or 0.032 μmol/l, respectively); S-(+)-α-methylhistamine (up to 10 μmol/l) as well as the selective H_1 receptor agonist (2-(2-thiazolyl)ethylamine) and the selective H_2 receptor agonist dimaprit (each up to 10 μmol/l) were ineffective. The H_3 receptor antagonist thioperamide abolished the inhibitory effect of histamine whereas the preferential H_1 receptor antagonist Dimetindene and the preferential H_2 receptor antagonist ranitidine were ineffective. In experiments on synaptosomes , histamine and R-(−)-α-methylhistamine inhibited NMDA-evoked tritium overflow, whereas 2-(2-thiazolyl)ethylamine or dimaprit had no effect. The inhibitory effect of histamine was abolished by thioperamide. When tritium overflow was stimulated by NMDA in the presence of ω-conotoxin GVIA (which by itself decreased the response to NMDA by about 55%), R-(−)-α-methylhistamine did not inhibit NMDA-evoked overflow. It is concluded that NMDA-evoked noradrenaline release in the cerebral cortex can be modulated by inhibitory H_3 receptors. NMDA receptors and H_3 receptors are both located presynaptically and may interact at the same noradrenergic varicosity. An unimpaired function of the N-type voltage-sensitive calcium channel probably is a prerequisite for the inhibition of NMDA-evoked noradrenaline release by H_3 receptor stimulation.
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N-methyl-D-aspartate (NMDA)-stimulated noradrenaline (NA) release in rat brain cortex is modulated by presynaptic H3-receptors.
Naunyn-Schmiedeberg's archives of pharmacology, 1994Co-Authors: Klaus Fink, Eberhard Schlicker, Manfred GöthertAbstract:In superfused rat brain cortex slices and synaptosomes preincubated with [3H]noradrenaline the effect of agonists or antagonists at presynaptic H3 receptors on NMDA-evoked [3H]noradrenaline release was investigated. In experiments on slices, histamine and the preferential H3 receptor agonist R-(−)-α-methylhistamine inhibited NMDA-evoked tritium overflow (IC20 values 0.27 μmol/l or 0.032 μmol/l, respectively); S-(+)-α-methylhistamine (up to 10 μmol/l) as well as the selective H1 receptor agonist (2-(2-thiazolyl)ethylamine) and the selective H2 receptor agonist dimaprit (each up to 10 μmol/l) were ineffective. The H3 receptor antagonist thioperamide abolished the inhibitory effect of histamine whereas the preferential H1 receptor antagonist Dimetindene and the preferential H2 receptor antagonist ranitidine were ineffective. In experiments on synaptosomes, histamine and R-(−)-α-methylhistamine inhibited NMDA-evoked tritium overflow, whereas 2-(2-thiazolyl)ethylamine or dimaprit had no effect. The inhibitory effect of histamine was abolished by thioperamide. When tritium overflow was stimulated by NMDA in the presence of ω-conotoxin GVIA (which by itself decreased the response to NMDA by about 55%), R-(−)-α-methylhistamine did not inhibit NMDA-evoked overflow. It is concluded that NMDA-evoked noradrenaline release in the cerebral cortex can be modulated by inhibitory H3 receptors. NMDA receptors and H3 receptors are both located presynaptically and may interact at the same noradrenergic varicosity. An unimpaired function of the N-type voltage-sensitive calcium channel probably is a prerequisite for the inhibition of NMDA-evoked noradrenaline release by H3 receptor stimulation.
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Histamine inhibits dopamine release in the mouse striatum via presynaptic H_3 receptors
Journal of Neural Transmission General Section JNT, 1993Co-Authors: Eberhard Schlicker, K. Fink, M. Detzner, Manfred GöthertAbstract:In superfused mouse striatal slices preincubated with [^3H] dopamine 25 nmol/l, the electrically (3 Hz) evoked tritium overflow was inhibited by histamine 10 μmol/l by 18%. The degree of inhibition was increased to 38% by haloperidol but not affected by (1) atropine, (2) reducing the stimulation frequency to 0.3 Hz or (3) increasing the concentration of [^3H]dopamine (used for preincubation) to 100 nmol/l. The effect of histamine was mimicked by the H_3 agonist R-(−)-α-methylhistamine; it was not affected by the H_1 antagonist Dimetindene and the H_2 antagonist ranitidine but abolished by the H_3 antagonist thioperamide. Tritium overflow evoked by Ca^2+ ions (introduced into Ca^2+free, K^+-rich medium containing tetrodotoxin) was not affected by histamine 10 μmol/l in the absence, but inhibited (by 30%) in the presence of haloperidol; the effect of histamine was abolished by thioperamide. In conclusion, the dopaminergic nerve terminals in the mouse striatum are endowed with presynaptic H_3 receptors. Simultaneous blockade of dopamine autoreceptors increases the extent of the H_3 receptor-mediated inhibition of dopamine release.
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histamine inhibits dopamine release in the mouse striatum via presynaptic h3 receptors
Journal of Neural Transmission, 1993Co-Authors: Eberhard Schlicker, Klaus Fink, M. Detzner, Manfred GöthertAbstract:In superfused mouse striatal slices preincubated with [3H] dopamine 25 nmol/l, the electrically (3 Hz) evoked tritium overflow was inhibited by histamine 10 μmol/l by 18%. The degree of inhibition was increased to 38% by haloperidol but not affected by (1) atropine, (2) reducing the stimulation frequency to 0.3 Hz or (3) increasing the concentration of [3H]dopamine (used for preincubation) to 100 nmol/l. The effect of histamine was mimicked by the H3 agonist R-(−)-α-methylhistamine; it was not affected by the H1 antagonist Dimetindene and the H2 antagonist ranitidine but abolished by the H3 antagonist thioperamide. Tritium overflow evoked by Ca2+ ions (introduced into Ca2+free, K+-rich medium containing tetrodotoxin) was not affected by histamine 10 μmol/l in the absence, but inhibited (by 30%) in the presence of haloperidol; the effect of histamine was abolished by thioperamide. In conclusion, the dopaminergic nerve terminals in the mouse striatum are endowed with presynaptic H3 receptors. Simultaneous blockade of dopamine autoreceptors increases the extent of the H3 receptor-mediated inhibition of dopamine release.
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Inhibition of noradrenaline release via NEM-sensitive H_3 receptors in the mouse brain cortex: more marked effect than in the rat brain
Agents and Actions, 1992Co-Authors: Eberhard Schlicker, A. Behling, G. Lümmen, Manfred GöthertAbstract:Mouse brain cortex slices preincubated with^3H-noradrenaline were superfused and the effect of histamine on the electrically (0.3 or 3 Hz) evoked tritium overflow was examined. The evoked overflow was inhibited by histamine and R-(−)-α-methylhistamine but not by 2-(2-thiazolyl)ethylamine and dimaprit. The effect of histamine was antagonized by thioperamide but not by dimethindene and ranitidine. The degree of inhibition produced by histamine was more marked at 0.3 than at 3 Hz and was attenuated by the α_2-adrenoceptor agonist talipexole (the former B-HT 920) but increased by phentolamine and the α_2-adrenoceptor antagonist rauwolscine. Pre-exposure of slices to N -ethylmaleimide attenuated the inhibitory effect of histamine. The results suggest that histamine inhibits nordrenaline release in the mouse brain cortex via H_3 receptors which interact with presynaptic α_2-adrenoceptor and may be coupled to a G (e.g. G_i or G_o) protein. The extent of H_3 receptor-mediated inhibition of nordrenaline release in the mouse brain is more marked than that in the rat brain.
Eberhard Schlicker - One of the best experts on this subject based on the ideXlab platform.
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Histaprodifen, methylhistaprodifen, and dimethylhistaprodifen are potent H1-receptor agonists in the pithed and in the anaesthetized rat.
Naunyn-Schmiedeberg's archives of pharmacology, 1999Co-Authors: Barbara Malinowska, Eberhard Schlicker, J. Piszcz, K. Kramer, Sigurd Elz, Walter SchunackAbstract:Selective H2- and H3-receptor agonists, exhibiting an at least tenfold higher potency than histamine itself at the respective receptors, have been known for several years. Selective H1-receptor agonists with a potency exceeding that of histamine have become available only recently; the most potent are methylhistaprodifen and dimethylhistaprodifen [Nα-methyl- and Nα,Nα-dimethyl-2-(3,3-diphenylpropyl)histamine, respectively] with 3.4- and 2.4-fold higher potencies than histamine in vitro (in the guinea-pig ileum). The aim of the present study was to examine whether these compounds and the parent compound histaprodifen are potent H1-receptor agonists in the pithed and in the anaesthetized rat. In pithed, vagotomized rats diastolic blood pressure was decreased by 2-(2-thiazolyl)ethanamine i.v. (which was used as a reference H1-receptor agonist) and by histaprodifen, methylhistaprodifen, and dimethylhistaprodifen; the maximum decrease was about 45 mmHg for each compound, and the potencies, expressed as pED50, the negative logarithm of the dose (in mole per kilogram body weight) eliciting a half-maximal response, were 7.23, 7.55, 8.43 and 8.12, respectively. The dose/response curves of the four compounds were shifted to the right to about the same extent by the H1-receptor antagonist Dimetindene (1 µmol/kg i.v.). The vasodepressor response was not affected by combined i.v. administration of the H2- and H3-receptor antagonists ranitidine and thioperamide, by combined i.v. administration of the α1- and α2-adrenoceptor antagonists prazosin and rauwolscine, and by the β-adrenoceptor antagonist propranolol i.v. but was attenuated by the inhibitor of NO synthase, Nω-nitro-l-arginine methyl ester i.v. In anaesthetized rats 2-(2-thiazolyl)ethanamine, histaprodifen, methylhistaprodifen and dimethylhistaprodifen i.v. also decreased diastolic blood pressure in a manner sensitive to Dimetindene i.v. Our data show that histaprodifen and, in particular, methyl- and dimethylhistaprodifen are highly potent H1-receptor agonists in vivo.
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N-methyl-d-aspartate (NMDA)-stimulated noradrenaline (NA) release in rat brain cortex is modulated by presynaptic H_3-receptors
Naunyn-Schmiedeberg's Archives of Pharmacology, 1994Co-Authors: K. Fink, Eberhard Schlicker, Manfred GöthertAbstract:In superfused rat brain cortex slices and synaptosomes preincubated with [^3H]noradrenaline the effect of agonists or antagonists at presynaptic H_3 receptors on NMDA-evoked [^3H]noradrenaline release was investigated. In experiments on slices , histamine and the preferential H_3 receptor agonist R-(−)-α-methylhistamine inhibited NMDA-evoked tritium overflow (IC_20 values 0.27 μmol/l or 0.032 μmol/l, respectively); S-(+)-α-methylhistamine (up to 10 μmol/l) as well as the selective H_1 receptor agonist (2-(2-thiazolyl)ethylamine) and the selective H_2 receptor agonist dimaprit (each up to 10 μmol/l) were ineffective. The H_3 receptor antagonist thioperamide abolished the inhibitory effect of histamine whereas the preferential H_1 receptor antagonist Dimetindene and the preferential H_2 receptor antagonist ranitidine were ineffective. In experiments on synaptosomes , histamine and R-(−)-α-methylhistamine inhibited NMDA-evoked tritium overflow, whereas 2-(2-thiazolyl)ethylamine or dimaprit had no effect. The inhibitory effect of histamine was abolished by thioperamide. When tritium overflow was stimulated by NMDA in the presence of ω-conotoxin GVIA (which by itself decreased the response to NMDA by about 55%), R-(−)-α-methylhistamine did not inhibit NMDA-evoked overflow. It is concluded that NMDA-evoked noradrenaline release in the cerebral cortex can be modulated by inhibitory H_3 receptors. NMDA receptors and H_3 receptors are both located presynaptically and may interact at the same noradrenergic varicosity. An unimpaired function of the N-type voltage-sensitive calcium channel probably is a prerequisite for the inhibition of NMDA-evoked noradrenaline release by H_3 receptor stimulation.
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N-methyl-D-aspartate (NMDA)-stimulated noradrenaline (NA) release in rat brain cortex is modulated by presynaptic H3-receptors.
Naunyn-Schmiedeberg's archives of pharmacology, 1994Co-Authors: Klaus Fink, Eberhard Schlicker, Manfred GöthertAbstract:In superfused rat brain cortex slices and synaptosomes preincubated with [3H]noradrenaline the effect of agonists or antagonists at presynaptic H3 receptors on NMDA-evoked [3H]noradrenaline release was investigated. In experiments on slices, histamine and the preferential H3 receptor agonist R-(−)-α-methylhistamine inhibited NMDA-evoked tritium overflow (IC20 values 0.27 μmol/l or 0.032 μmol/l, respectively); S-(+)-α-methylhistamine (up to 10 μmol/l) as well as the selective H1 receptor agonist (2-(2-thiazolyl)ethylamine) and the selective H2 receptor agonist dimaprit (each up to 10 μmol/l) were ineffective. The H3 receptor antagonist thioperamide abolished the inhibitory effect of histamine whereas the preferential H1 receptor antagonist Dimetindene and the preferential H2 receptor antagonist ranitidine were ineffective. In experiments on synaptosomes, histamine and R-(−)-α-methylhistamine inhibited NMDA-evoked tritium overflow, whereas 2-(2-thiazolyl)ethylamine or dimaprit had no effect. The inhibitory effect of histamine was abolished by thioperamide. When tritium overflow was stimulated by NMDA in the presence of ω-conotoxin GVIA (which by itself decreased the response to NMDA by about 55%), R-(−)-α-methylhistamine did not inhibit NMDA-evoked overflow. It is concluded that NMDA-evoked noradrenaline release in the cerebral cortex can be modulated by inhibitory H3 receptors. NMDA receptors and H3 receptors are both located presynaptically and may interact at the same noradrenergic varicosity. An unimpaired function of the N-type voltage-sensitive calcium channel probably is a prerequisite for the inhibition of NMDA-evoked noradrenaline release by H3 receptor stimulation.
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Histamine inhibits dopamine release in the mouse striatum via presynaptic H_3 receptors
Journal of Neural Transmission General Section JNT, 1993Co-Authors: Eberhard Schlicker, K. Fink, M. Detzner, Manfred GöthertAbstract:In superfused mouse striatal slices preincubated with [^3H] dopamine 25 nmol/l, the electrically (3 Hz) evoked tritium overflow was inhibited by histamine 10 μmol/l by 18%. The degree of inhibition was increased to 38% by haloperidol but not affected by (1) atropine, (2) reducing the stimulation frequency to 0.3 Hz or (3) increasing the concentration of [^3H]dopamine (used for preincubation) to 100 nmol/l. The effect of histamine was mimicked by the H_3 agonist R-(−)-α-methylhistamine; it was not affected by the H_1 antagonist Dimetindene and the H_2 antagonist ranitidine but abolished by the H_3 antagonist thioperamide. Tritium overflow evoked by Ca^2+ ions (introduced into Ca^2+free, K^+-rich medium containing tetrodotoxin) was not affected by histamine 10 μmol/l in the absence, but inhibited (by 30%) in the presence of haloperidol; the effect of histamine was abolished by thioperamide. In conclusion, the dopaminergic nerve terminals in the mouse striatum are endowed with presynaptic H_3 receptors. Simultaneous blockade of dopamine autoreceptors increases the extent of the H_3 receptor-mediated inhibition of dopamine release.
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Identification of endothelial H_1, vascular H_2 and cardiac presynaptic H_3 receptors in the pithed rat
Naunyn-Schmiedeberg's Archives of Pharmacology, 1993Co-Authors: Barbara Malinowska, Eberhard SchlickerAbstract:In pithed and vagotomized rats the effects of the H_3 receptor agonist R-(−)-α-methylhistamine, the H_1 receptor agonist 2-(2-thiazolyl)ethylamine and the H_2 receptor agonist dimaprit on basal diastolic blood pressure, basal heart rate and the electrically induced rise in heart rate were examined. Basal diastolic blood pressure was not altered by low, but increased by high doses of R-(−)-α-methylhistamine; the latter effect was not affected by selective H_1, H_2 or H_3 receptor antagonists and by prazosin, but was attenuated by rauwolscine. Rauwolscine also unmasked a vasodepressor response to R-(−)-α-methylhistamine not affected by the H_3 receptor antagonist thioperamide, but counteracted by the H_1 receptor antagonist Dimetindene or the H_2 receptor antagonist ranitidine. The vasodepressor responses to 2-(2-thiazolyl)ethylamine and dimaprit were antagonized by Dimetindene and ranitidine, respectively. The vasodepressor response to 2-(2-thiazolyl)ethylamine was not altered by indomethacin, but reduced by an inhibitor of endothelial nitric oxide synthase, N^ω-nitro-L-arginine methyl ester (which, by itself, markedly increased blood pressure). Both drug tools did not alter the effect of dimaprit. Basal heart rate was not affected by 2-(2-thiazolyl)ethylamine (examined after administration of propranolol), dimaprit and R-(−)-α-methylhistamine. The electrically induced increase in heart rate (studied in animals which had received rauwolscine) was decreased by R-(−)-α-methylhistamine but not affected by 2-(2-thiazolyl)ethylamine and dimaprit. The effect of R-(−)-α-methylhistamine was abolished by thioperamide. R-(−)-α-methylhistamine did not influence the increase in heart rate produced by isoprenaline. In conclusion, the pithed rat offers the opportunity to study cardiac presynaptic H_3 receptors, endothelial H_1 receptors and vascular H_2 receptors in the same experimental model. Cardiac presynaptic H_1 and H_2 receptors as well as postsynaptic H_3 receptors in the heart and in the resistance vessels were not found. R-(−)-α-methylhistamine is a weak agonist at α_2, H_1 and H_2 receptors.
Gunter J. Sturm - One of the best experts on this subject based on the ideXlab platform.
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cd203c based basophil activation test in allergy diagnosis characteristics and differences to cd63 upregulation
Cytometry Part B-clinical Cytometry, 2010Co-Authors: Eva M. Sturm, Akos Heinemann, Werner Aberer, Bettina Kranzelbinder, Andrea Groseljstrele, Gunter J. SturmAbstract:Background: The basophil activation test (BAT) based on CD203c upregulation has been validated as a reliable tool for the diagnosis of IgE-mediated allergies. Nevertheless, CD203c-based BAT is hardly comparable with that of CD63-based tests, as the mechanisms of CD203c versus CD63 induction differ considerably. The aim of the present study was to identify potent influencing factors of the CD203cbased BAT and to emphasize differences between CD63 and CD203c detection. Methods: CD203c-based BAT was determined in 82 healthy controls and in 79 allergic patients. The effects of interleukin (IL)-3 and degranulation enhancing substances were investigated and compared with CD63 upregulation. Furthermore, the influence of different storage conditions and incubation times was evaluated and the impact of antiallergic drugs on the test results was assessed. Results: CD203c and CD63 expression was rapidly upregulated reaching a maximum after 20–30 min. Basophil CD203c upregulation assayed after storage times up to 48 h declined already after 4 h. IL-3 treatment increased CD203c and CD63 baseline levels and decreased basophil CD203c responses in a dose-dependent manner. In contrast, cytochalasin B and latrunculin B did not affect CD203c responses but decreased CD63-based BAT. Finally, therapeutic concentrations of Dimetindene and desloratadine did not affect CD203c upregulation. Conclusion: CD203c-based basophil activation test should be performed preferentially within 4 h after taking the blood samples. Priming and degranulation-enhancing factors are not required for CD203cbased BAT. In contrast to skin testing, CD203c-based BAT can be performed in patients undergoing antiallergic treatment. V C 2010 International Clinical Cytometry Society
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CD203c‐based basophil activation test in allergy diagnosis: Characteristics and differences to CD63 upregulation
Cytometry. Part B Clinical cytometry, 2010Co-Authors: Eva M. Sturm, Akos Heinemann, Werner Aberer, Bettina Kranzelbinder, Andrea Groselj-strele, Gunter J. SturmAbstract:Background: The basophil activation test (BAT) based on CD203c upregulation has been validated as a reliable tool for the diagnosis of IgE-mediated allergies. Nevertheless, CD203c-based BAT is hardly comparable with that of CD63-based tests, as the mechanisms of CD203c versus CD63 induction differ considerably. The aim of the present study was to identify potent influencing factors of the CD203cbased BAT and to emphasize differences between CD63 and CD203c detection. Methods: CD203c-based BAT was determined in 82 healthy controls and in 79 allergic patients. The effects of interleukin (IL)-3 and degranulation enhancing substances were investigated and compared with CD63 upregulation. Furthermore, the influence of different storage conditions and incubation times was evaluated and the impact of antiallergic drugs on the test results was assessed. Results: CD203c and CD63 expression was rapidly upregulated reaching a maximum after 20–30 min. Basophil CD203c upregulation assayed after storage times up to 48 h declined already after 4 h. IL-3 treatment increased CD203c and CD63 baseline levels and decreased basophil CD203c responses in a dose-dependent manner. In contrast, cytochalasin B and latrunculin B did not affect CD203c responses but decreased CD63-based BAT. Finally, therapeutic concentrations of Dimetindene and desloratadine did not affect CD203c upregulation. Conclusion: CD203c-based basophil activation test should be performed preferentially within 4 h after taking the blood samples. Priming and degranulation-enhancing factors are not required for CD203cbased BAT. In contrast to skin testing, CD203c-based BAT can be performed in patients undergoing antiallergic treatment. V C 2010 International Clinical Cytometry Society
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The basophil activation test in the diagnosis of allergy: technical issues and critical factors.
Allergy, 2009Co-Authors: Gunter J. Sturm, Akos Heinemann, Eva M. Sturm, Bettina Kranzelbinder, Andrea Groselj-strele, Werner AbererAbstract:Background: The basophil activation test (BAT) is a widely validated and reliable tool especially for the diagnosis of hymenoptera venom allergy. Nevertheless, several pitfalls have to be considered and outcomes may differ because of diverse in-house protocols and commercially available kits. We aimed to identify the factors that may influence results of the CD63-based BAT. Methods: Basophil responses to monoclonal anti-IgE (clone E124.2.8) and bee and wasp venom were determined by BAT based on CD63. The effect of stimulating factors such as, IL-3, cytochalasin B and prewarming of the samples was investigated. Furthermore, we compared two different flow cytometer systems and evaluated the influence of storage time, different staining protocols and anti-allergic drugs on the test results. Results: Interleukin-3 enhanced the reactivity of basophils at 300 pM, but not at 75 and 150 pM. Prewarming of samples and reagents did not affect basophil reactivity. CD63 expression assayed after storage time of up to 48 h showed that basophil reactivity already started to decline after 4 h. Basophils stained with HLA-DR-PC5 and CD123-PE antibodies gated as HLA-DRneg/CD123pos cells showed the highest reactivity. No effect on test outcomes was observed at therapeutic doses of Dimetindene and desloratadine. Finally, slight differences in the percentage of activated basophils, depending on the cytometer system used, were found. Conclusion: Basophil activation test should be performed as early as possible after taking the blood sample, preferably within 4 h. In contrast to the skin test, BAT can be performed in patients undergoing treatment with antihistamines. For reasons of multiple influencing factors, BAT should be performed only at validated laboratories.
Klaus Fink - One of the best experts on this subject based on the ideXlab platform.
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N-methyl-D-aspartate (NMDA)-stimulated noradrenaline (NA) release in rat brain cortex is modulated by presynaptic H3-receptors.
Naunyn-Schmiedeberg's archives of pharmacology, 1994Co-Authors: Klaus Fink, Eberhard Schlicker, Manfred GöthertAbstract:In superfused rat brain cortex slices and synaptosomes preincubated with [3H]noradrenaline the effect of agonists or antagonists at presynaptic H3 receptors on NMDA-evoked [3H]noradrenaline release was investigated. In experiments on slices, histamine and the preferential H3 receptor agonist R-(−)-α-methylhistamine inhibited NMDA-evoked tritium overflow (IC20 values 0.27 μmol/l or 0.032 μmol/l, respectively); S-(+)-α-methylhistamine (up to 10 μmol/l) as well as the selective H1 receptor agonist (2-(2-thiazolyl)ethylamine) and the selective H2 receptor agonist dimaprit (each up to 10 μmol/l) were ineffective. The H3 receptor antagonist thioperamide abolished the inhibitory effect of histamine whereas the preferential H1 receptor antagonist Dimetindene and the preferential H2 receptor antagonist ranitidine were ineffective. In experiments on synaptosomes, histamine and R-(−)-α-methylhistamine inhibited NMDA-evoked tritium overflow, whereas 2-(2-thiazolyl)ethylamine or dimaprit had no effect. The inhibitory effect of histamine was abolished by thioperamide. When tritium overflow was stimulated by NMDA in the presence of ω-conotoxin GVIA (which by itself decreased the response to NMDA by about 55%), R-(−)-α-methylhistamine did not inhibit NMDA-evoked overflow. It is concluded that NMDA-evoked noradrenaline release in the cerebral cortex can be modulated by inhibitory H3 receptors. NMDA receptors and H3 receptors are both located presynaptically and may interact at the same noradrenergic varicosity. An unimpaired function of the N-type voltage-sensitive calcium channel probably is a prerequisite for the inhibition of NMDA-evoked noradrenaline release by H3 receptor stimulation.
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histamine inhibits dopamine release in the mouse striatum via presynaptic h3 receptors
Journal of Neural Transmission, 1993Co-Authors: Eberhard Schlicker, Klaus Fink, M. Detzner, Manfred GöthertAbstract:In superfused mouse striatal slices preincubated with [3H] dopamine 25 nmol/l, the electrically (3 Hz) evoked tritium overflow was inhibited by histamine 10 μmol/l by 18%. The degree of inhibition was increased to 38% by haloperidol but not affected by (1) atropine, (2) reducing the stimulation frequency to 0.3 Hz or (3) increasing the concentration of [3H]dopamine (used for preincubation) to 100 nmol/l. The effect of histamine was mimicked by the H3 agonist R-(−)-α-methylhistamine; it was not affected by the H1 antagonist Dimetindene and the H2 antagonist ranitidine but abolished by the H3 antagonist thioperamide. Tritium overflow evoked by Ca2+ ions (introduced into Ca2+free, K+-rich medium containing tetrodotoxin) was not affected by histamine 10 μmol/l in the absence, but inhibited (by 30%) in the presence of haloperidol; the effect of histamine was abolished by thioperamide. In conclusion, the dopaminergic nerve terminals in the mouse striatum are endowed with presynaptic H3 receptors. Simultaneous blockade of dopamine autoreceptors increases the extent of the H3 receptor-mediated inhibition of dopamine release.
K. Tepetes - One of the best experts on this subject based on the ideXlab platform.
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Adhesion Prevention to Polypropylene Meshes Using Combined Icodextrin Four Percent and Dimetindene Maleate
The Journal of surgical research, 2018Co-Authors: Konstantinos Bouliaris, Eftihia K. Asprodini, Panagiotis Liakos, Alexandros Diamantis, Georgios Koukoulis, Christina Befani, Stella Tzika, K. TepetesAbstract:Abstract Background The use of surgical meshes in ventral hernia repair has significantly reduced hernia recurrence rates. However, when placed intraperitoneally prosthetic materials can trigger the development of peritoneal adhesions. The present experimental study evaluated the combined icodextrin 4% and Dimetindene maleate treatment in preventing peritoneal adhesion formation to polypropylene and titanium-coated polypropylene meshes. Materials and methods Sixty female white rabbits were divided into four groups. A 2 × 2 cm piece of mesh was fixed to intact peritoneum in all animals through a midline laparotomy. A lightweight polypropylene mesh was implanted in groups 1 and 2 and a titanium-coated polypropylene mesh in groups 3 and 4. Groups 2 and 4 were treated, intraoperatively, with intravenous Dimetindene maleate (0.1 mg/kg) and intraperitoneal solution of icodextrin 4% (20 mL/kg) and for the next 6 d with Dimetindene maleate intramuscularly. The observation period lasted 15 d. Adhesion scores, percentage of mesh affected surface, tissue hydroxyproline levels, and tissue histopathology were examined. Results All animals in group 1 and 57% of animals in group 3 presented postoperative adhesions. The combination of antiadhesives significantly reduced the extent and severity of adhesions as well as the hydroxyproline levels in groups 2 and 4 compared with groups 1 and 3. On microscopic evaluation, animals in group 1 exhibited higher inflammation scores compared with group 2, whereas animals in groups 2 and 4 had better mesotheliazation compared with groups 1 and 3. Conclusions The combined administration of icodextrin 4% and Dimetindene maleate reduces the extent and severity of adhesions and may be successfully used to prevent adhesion formation after mesh intraperitoneal placement.
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Role of Histamine in Altering Fluid Recycling in Normal and Post-Traumatic Rabbit Peritoneum
Inflammation, 2014Co-Authors: Vasileios K. Kouritas, K. Tepetes, Michalis Spyridakis, Konstantina V. Theodosopoulou, Konstantinos I. Gourgoulianis, Paschalis A. Molyvdas, Chrisi HatzoglouAbstract:This study aims to investigate if histamine induces electrochemical alterations in the normal and post-traumatic peritoneum. Peritoneal rabbit specimens were obtained before surgery and 10 days post-operatively and were mounted in Ussing chambers. Histamine solutions were added facing the intra-peritoneal and outer-peritoneal surface. Dimetindene maleate-, cetirizine-, and ranitidine-pretreated specimens were used to investigate histamine receptor involvement, whereas amiloride- and ouabain-pretreated specimens were used to investigate ion transportation blockage involvement. Trans-mesothelial resistance ( R _ TM ) was determined. Histamine-increased R _ TM intra-peritoneally and decreased it outer-peritoneally. A less intense effect was induced in post-traumatic specimens. Dimetindene maleate, cetirizine, amiloride, and ouabain totally inhibited this effect, whereas ranitidine only had a partial effect. Histamine induces electrochemical alterations in the normal and post-operative peritoneum. This effect is mediated by interaction with histamine receptors, hindering the normal process of ion trans-mesothelial transportation.
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Matrix Metaloproteinase-2 and -9 Serum Levels as Potential Markers of Intraperitoneal Adhesions
Journal of investigative surgery : the official journal of the Academy of Surgical Research, 2013Co-Authors: Gregory Christodoulidis, M. Spyridakis, Irene Tsilioni, Theodoros Kiropoulos, Smaragda Oikonomidi, George K. Koukoulis, K. TepetesAbstract:ABSTRACTObjective: To assess the value of matrix metalloproteinases-2 (MMP-2) and -9 (MMP-9) as prognostic serum markers for intraperitoneal adhesions. Background: Postoperative adhesions are associated with serious complications responsible for increased patient's morbidity. Methods: Forty-eight rabbits were used and randomized into groups A, B, C, and D. Abdominal laparotomy and experimental adhesion formation model was carried out. In group A, 60 mL of N/S 0.9% were instilled intraperitoneally, in group B 60 mL of icodextrin 4% were instilled intraperitoneally, in group C 0.1 mL/kg of Dimetindene maleate were administered intravenously, and in group D both agents were administered. Prior to euthanasia 0.5 mL of blood was obtained. The type, the surface area of adhesions, and serum concentration of MMPs were assessed. Results: The mean surface area and Zuhlke classification of adhesions of groups B, C, and D has been proved to be significantly lower compared to group A. Serum MMP-2 levels were significa...
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Effect of histamine on the electrophysiology of the human parietal pleura.
Molecular and cellular endocrinology, 2010Co-Authors: V. K. Kouritas, K. Tepetes, Konstantinos I. Gourgoulianis, A. Tsantsaridou, Nikolaos Tsilimingas, Chrissi HatzoglouAbstract:Abstract Introduction Histamine is involved in the pathogenesis of numerous diseases and regulates the permeability of different tissues. The aim of this study is to investigate the effects of histamine on the electrophysiology of human parietal pleura and the underlying mechanisms involved. Materials and methods Pleural specimens were obtained from patients subjected to thoracic surgery and were mounted in Ussing chambers. Histamine solutions (1 μM to 1 mM) were applied in native and pretreated specimens with Dimetindene maleate, cetirizine, ranitidine, amiloride and ouabain. Trans-mesothelial resistance was determined (RTM). Results Histamine induced a rapid RTM increase on the mesothelial (p = 0.008) and a decrease on the interstitial surface (p = 0.029). This effect was dose-dependent and was totally abolished by Dimetindene maleate, cetirizine and amiloride and partially by ranitidine and ouabain. Conclusions Histamine induces acute electrochemical changes in human pleura mainly via interaction with the H1 and partially with the H2 histamine receptors. It also interferes with trans-cellular permeability and therefore may participate in pleural fluid recycling.
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Permeability alterations after surgical trauma in normal rabbit peritoneum.
European surgical research. Europaische chirurgische Forschung. Recherches chirurgicales europeennes, 2010Co-Authors: V. K. Kouritas, K. Tepetes, M. Spyridakis, Konstantinos I. Gourgoulianis, G. Christodoulides, Maria Ioannou, Chrissi HatzoglouAbstract:Background: To investigate whether surgical trauma in a rabbit adhesion formation model and the administration of normal saline (N/S), icodextrin (ID) and/or Dimetindene maleate (DM) changes the permeability of the normal rabbit parietal peritoneum. Materials and Methods: A total of 45 female rabbits were operated on for adhesion formation and were euthanized 10 days later. In some rabbits, ID or N/S was instilled intraabdominally during operation, whereas in others DM was infused intravenously. In others, ID plus DM or no agent was used. Specimens were obtained postoperatively and were mounted between Ussing chambers. Amiloride was used to investigate Na+ channels. Transmesothelial resistance (RTM) was determined as a permeability indicator. Results: Amiloride increased the RTM of both surfaces. Surgical trauma increased RTM and partially inhibited the effect of amiloride. ID and N/S increased RTM and inhibited the effect of amiloride. Use of DM did not change RTM and did not inhibit the effect of amiloride. Use of ID plus DM slightly increased RTM, but the effect of amiloride was blocked. Conclusions: Surgical trauma impairs the permeability of the normal rabbit parietal peritoneum. ID or N/S surmounted this effect, but DM did not, suggesting that surgical trauma is a diffuse process. Antiadhesion measures influence peritoneal physiology.