European Journal of Pharmacology: Environmental Toxicology and Pharmacology最新文献

{"title":"Effect of capsaicin on membrane currents in cultured vascular smooth muscle cells of rat aorta","authors":"Yi-Ching Lo ,&nbsp;Sheng-Nan Wu ,&nbsp;Jiunn-Ren Wu ,&nbsp;Ing-Jun Chen","doi":"10.1016/0926-6917(95)90039-X","DOIUrl":"10.1016/0926-6917(95)90039-X","url":null,"abstract":"<div><p>The application of capsaicin (1 μM) produced a minor relaxant effect in endothelium-denuded rat aortae. However, capsaicin caused a greater relaxation of blood vessels precontracted with high K⁺ or phenylephrine. The effects of capsaicin on the ionic currents were also examined in A7r5 vascular smooth muscle cells. The tight-seal whole-cell voltage clamp technique was used. Capsaicin inhibited the Ba²⁺ inward current (I_Ba) through the voltage-dependent L-type Ca²⁺ channel in a concentration-dependent fashion, whereas calcitonin gene-related peptide and phenylephrine produced a minor increase in I_Ba. Capsaicin did not alter the overall shape of current-voltage relationship of I_Ba. However, capsaicin (3 μM) shifted the quasi-steady-state inactivation curve of I_Ba to more negative membrane potential by about 5 mV. These effects of capsaicin on I_Ba were reversible. In addition, capsaicin had inhibitory effects on voltage dependent K⁺ currents. These results suggest that inhibition of the voltage-dependent L-type Ca²⁺ channel is involved in the capsaicin-induced relaxation of the vascular smooth muscle, whereas capsaicin-induced inhibition of voltage-dependent K⁺ channels might produced an increase in cell excitability.</p></div>","PeriodicalId":100501,"journal":{"name":"European Journal of Pharmacology: Environmental Toxicology and Pharmacology","volume":"292 3","pages":"Pages 321-328"},"PeriodicalIF":0.0,"publicationDate":"1995-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0926-6917(95)90039-X","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18548437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The tyramine-labelled vesicular transporter for dopamine: a putative target of pesticides and neurotoxins","authors":"Andrea Vaccari,&nbsp;PierLuigi Saba","doi":"10.1016/0926-6917(95)90037-3","DOIUrl":"10.1016/0926-6917(95)90037-3","url":null,"abstract":"<div><p>This study defined the ability of a large sample of heterogeneous pesticides and neurotoxins to interact with the [³H]tyramine-labelled vesicular transporter of dopamine in rat striatum. Botanical (with rotenone as the most potent), and organochlorine (Kepone) insecticides, as well as fungicides (Zineb), as a whole, consistently inhibited [³H]tyramine binding, with <em>K</em>_i values ranging from 5 nM to 10 μM. ATP/Mg²⁺-dependent [³H]tyramine uptake to purified striatal synaptic vesicles was also inhibited by rotenone. Organophosphate and carbamate insecticides, and miscellaneous herbicides poorly antagonized [³H]tyramine binding, yielding <em>K</em>_i values exceeding 10 μM. Several, though not all, of the best recognized central neurotoxins tested were major binding antagonists. Their rank order of potency was 1-methyl-4-phenylpyridinium ion (MPP⁺) &gt; trimethyltin ≥ 6-hydroxydopamine &gt; <em>N</em>-(2-chloroethyl)-<em>N</em>-ethyl-2-bromobenzylamine (DSP-4) &gt; 1-methyl-4-pheny;-1,2,3,6-tetrahydropyridine (MPTP), with <em>K</em>_i values ranging from 35 nM to 3 μM. Overall, the potent interaction of selected pesticides and chemicals with the vesicular transporter for dopamine, although, by itself, not synonymous with neurotoxicity, would argue for a likely impairment of transmitter homeostasis, or the putative formation of neurodegenerative toxin pools.</p></div>","PeriodicalId":100501,"journal":{"name":"European Journal of Pharmacology: Environmental Toxicology and Pharmacology","volume":"292 3","pages":"Pages 309-314"},"PeriodicalIF":0.0,"publicationDate":"1995-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0926-6917(95)90037-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18796284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of N-acetyl-L-cysteine on sepsis in mice","authors":"Pia Villa ,&nbsp;Pietro Ghezzi","doi":"10.1016/0926-6917(95)90043-8","DOIUrl":"10.1016/0926-6917(95)90043-8","url":null,"abstract":"<div><p>The effect of the antioxidant <span><math><mtext>N-</mtext><mtext>acetyl-</mtext><mtext>L</mtext><mtext>-cysteine</mtext></math></span> was studied in a model of polymicrobial sepsis induced in CD-1 mice by cecal ligation and puncture. <span><math><mtext>N-</mtext><mtext>acetyl-</mtext><mtext>L</mtext><mtext>-cysteine</mtext></math></span> significantly improved survival during the 6 days following sepsis induction and caused lower liver toxicity. This effect was not related to free radicals generated by xanthine oxidase which was significantly induced in liver after cecal ligation and puncture. A specific inhibitor of xanthine oxidase, allopurinol, significantly reduced this enzyme and reduced the early survival rate. The effect of <span><math><mtext>N-</mtext><mtext>acetyl-</mtext><mtext>L</mtext><mtext>-cysteine</mtext></math></span> was not related either to a reduction in tumor necrosis factor production or to a modulation of nitrites or to liver glutathione content. These results show that the induction of xanthine oxidase is not deleterious in this model of sepsis and suggest that <span><math><mtext>N-</mtext><mtext>acetyl-</mtext><mtext>L</mtext><mtext>-cysteine</mtext></math></span> works as a direct antioxidant and scavenger of free radicals generated from other sources.</p></div>","PeriodicalId":100501,"journal":{"name":"European Journal of Pharmacology: Environmental Toxicology and Pharmacology","volume":"292 3","pages":"Pages 341-344"},"PeriodicalIF":0.0,"publicationDate":"1995-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0926-6917(95)90043-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18796289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on mitochondrial respiration in ischemic rat hearts","authors":"Kumi Satoh,&nbsp;Kazuo Ichihara","doi":"10.1016/0926-6917(95)90032-2","DOIUrl":"10.1016/0926-6917(95)90032-2","url":null,"abstract":"<div><p>The aim of the present study was to examine the effects of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors on mitochondrial respiration in ischemic rat hearts, and to compare the effects between water-soluble pravastatin and lipid-soluble simvastatin. Either vehicle (0.5% carboxymethyl cellulose), pravastatin (2 or 4 mg/kg per day), or simvastatin (1 or 2 mg/kg per day) was orally administered for 3 weeks. Ischemia was induced by ligating the aorta for 60 min in anesthetized open chest rats under artificial respiration. The hearts were removed, mitochondria were isolated, and the respiration was determined by polarography using glutamate and succinate as substrates. When succinate was used as a substrate, the ADP-stimulated respiration (QO₃) and ATP production per unit oxygen (ADP/O ratio) were decreased by ischemia. The decreases in QO₃ and ADP/O ratio in the pravastatin-and simvastatin-treated groups appeared to be more prominent than those in the vehicle-treated group. This was especially true in the simvastatin-treated group. The ADP-limited respiration (QO₄) with succinate in the vehicle-treated heart was slightly increased by ischemia, while that in the pravastatin- or simvastatin-treated hearts was decreased. In conclusion, HMG-CoA reductase inhibitors may result in worsening of myocardial mitochondrial respiration during ischemia.</p></div>","PeriodicalId":100501,"journal":{"name":"European Journal of Pharmacology: Environmental Toxicology and Pharmacology","volume":"292 3","pages":"Pages 271-275"},"PeriodicalIF":0.0,"publicationDate":"1995-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0926-6917(95)90032-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18796356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Free radicals irreversibly decrease Ca2+ currents in isolated guinea-pig ventricular myocytes","authors":"Jaswinder S. Gill,&nbsp;William J. McKenna,&nbsp;A.John Camm","doi":"10.1016/0926-6917(95)90042-X","DOIUrl":"10.1016/0926-6917(95)90042-X","url":null,"abstract":"<div><p>The effects of free radicals on voltage-gates Ca²⁺ currents (<em>I</em>_Ca) were investigated in single guinea-pig ventricular myocytes using the whole-cell clamp technique. <em>I</em>_Ca was measured in the baseline state and after the application of free radicals from cumene hydroperoxide or generated from the addition of purine to xanthine oxidase. <em>I</em>_Ca decreased from 846 ± 533 (S.D.) pA to 688 ± 444 pA (<em>n</em> = 7, <em>P</em> &lt; 0.05) in the presence of 100 μM cumene hydroperoxide and from 708 ± 157 pA to 457 ± 163 pA(<em>n</em> = 5, <em>P</em> &lt; 0.0001) in the presence of 500 μM cumene hydroperoxide. <em>I</em>_Ca also decreased from 1303 ± 560 pA to 965 ± 360 pA in the presence of the free radical generating system (2.3 mM purine plus 20 U/l xanthine oxidase). The reduced <em>I</em>_Ca could not be restored by washing for up to 5 min using normal recording solution. We conclude that <em>I</em>_Ca is decreased in the presence of cumene hydroperoxide and an oxygen-derived free radical generating system in single guinea-pig ventricular myocytes. The cellular Ca²⁺ overload observed in free radical mediated reperfusion injury is therefore unlikely to result from an increase in sacrolemmal Ca²⁺ entry via voltage-gated Ca²⁺ channels.</p></div>","PeriodicalId":100501,"journal":{"name":"European Journal of Pharmacology: Environmental Toxicology and Pharmacology","volume":"292 3","pages":"Pages 337-340"},"PeriodicalIF":0.0,"publicationDate":"1995-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0926-6917(95)90042-X","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18796288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Key word index","authors":"","doi":"10.1016/0926-6917(95)90046-2","DOIUrl":"https://doi.org/10.1016/0926-6917(95)90046-2","url":null,"abstract":"","PeriodicalId":100501,"journal":{"name":"European Journal of Pharmacology: Environmental Toxicology and Pharmacology","volume":"292 3","pages":"Pages 353-359"},"PeriodicalIF":0.0,"publicationDate":"1995-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0926-6917(95)90046-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92051242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of mitochondrial complexes I and IV by 6-hydroxydopamine","authors":"Yelena Y. Glinka,&nbsp;Moussa B.H. Youdim","doi":"10.1016/0926-6917(95)90040-3","DOIUrl":"10.1016/0926-6917(95)90040-3","url":null,"abstract":"<div><p>The enzymes of mitochondrial respiratory chain, NADH dehydrogenase (complex I) and cytochrome c oxidase (complex IV), were completely inhibited by 6-hydroxydopamine with IC₅₀ = 10.5 <em>μ</em>M and IC₅₀ = 34 <em>μ</em>M respectively. The enzyme inhibition was insensitive to the change of NADH or cytochrome c concentrations. The extent of complex I inhibition decreased as a consequence of both non-enzymatic and monoamine oxidase-catalyzed oxidation of 6-hydroxydopamine. Monoamine oxidase A and B inhibitors, tranylcypromine and clorgyline but not <em>l</em>-deprenyl increased the extent of 6-hydroxydopamine induced inhibition of complex I. Thus, 6-hydroxydopamine itself and not its oxidation products may be responsible for the neurotoxicity of this agent via inhibition of respiratory chain enzymes.</p></div>","PeriodicalId":100501,"journal":{"name":"European Journal of Pharmacology: Environmental Toxicology and Pharmacology","volume":"292 3","pages":"Pages 329-332"},"PeriodicalIF":0.0,"publicationDate":"1995-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0926-6917(95)90040-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18796286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pertussis and cholera toxins modulate κ-opioid receptor agonists-induced hypothermia and gut inhibition","authors":"Vijay Kumar Shukla,&nbsp;Herman Turndorf,&nbsp;Mylarrao Bansinath","doi":"10.1016/0926-6917(95)90035-7","DOIUrl":"10.1016/0926-6917(95)90035-7","url":null,"abstract":"<div><p>In mice pretreated intracerebroventricularly (i.c.v.) with either saline (1 μl/mouse), pertussis (1 μg/mouse) or cholera (2.5 μg/mouse) toxins, effect of κ-opioid receptor agonists on the colonic temperature and charcoal meal transit time were assessed. The κ-opioid receptor agonist, <em>trans</em>-(+)-3,4-dichloro-<em>N</em>-methyl-[2-(1-pyrrolidinyl)cyclohexyl]-benzeneacetamide methane sulfonate hydrate (U-50488H, 50, 100 and 200 μg/mouse, i.c.v.) produced dose dependent hypothermia. Pertussis toxin pretreatment (72 and/or 144 h before) antagonized (<em>P</em> &lt; 0.05) the hypothermic effect of U-50488H (100 μg/mouse) and (±)-<em>trans</em>-<em>N</em>-methyl-<em>N</em>-[2-(1-pyrrolidinyl)cyclohexyl[benz[b]-thio-phene-4-acetamide (PD 117302, 30 μg/mouse). In contrast, cholera toxin pretreatment (48 and/or 96 h before) did not antagonize the hypothermic effect of the κ-opioid receptor agonists. Moreover, both i.c.v. and intrathecal (i.t.) administration of κ-opioid receptor agonists, U-50488H, {[5<em>R</em>-(5<em>α</em>,7<em>α</em>,8<em>β</em>)]-(±)-<em>N</em>-methyl-<em>N</em>-[7-(1-pyrrolidinyl)-1-oxaspirol[4,5]dec-8-yl]-benzeneacetamide} (U-65593) and PD 117302, produced dose dependent inhibition of the charcoal meal transit. Cholera toxin pretreatment (48 and 96 h before) augmented (<em>P</em> &lt; 0.05) the antitransit effect of i.c.v. administered U-50488H (100 μg/mouse), U-69593 (100 μg/mouse) and PD 117302 (50 μg/mouse). However, pertussis toxin previous pretreatment did not affect the gastrointestinal inhibitory effect of the κ-opioid receptors agonists. The present results extend our previous results on the affect of κ-selective agonists on gastrointestinal motility and indicate, like the prototype opiate agonist morphine, κ-opioid receptor agonists are effective in inhibiting the gastrointestinal motility when administered either by intrathecal or intracerebroventricular routes. Thus, for the antitransit effect of κ-opioid receptor agonists, both spinal and supra spinal site could be implicated. Furthermore, these results also suggest that pertussis and cholera toxin-sensitive transducer G-proteins may be involved in the central κ-opioid receptor mediated hypothermia and gastrointestinal transit inhibition respectively.</p></div>","PeriodicalId":100501,"journal":{"name":"European Journal of Pharmacology: Environmental Toxicology and Pharmacology","volume":"292 3","pages":"Pages 293-299"},"PeriodicalIF":0.0,"publicationDate":"1995-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0926-6917(95)90035-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18796359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"N-Acetylcysteine protects against age-related decline of oxidative phosphorylation in liver mitochondria","authors":"Jaime Miquel ,&nbsp;María L. Ferrándiz ,&nbsp;Emilio De Juan ,&nbsp;Immaculada Sevila ,&nbsp;Marcos Martínez","doi":"10.1016/0926-6917(95)90041-1","DOIUrl":"10.1016/0926-6917(95)90041-1","url":null,"abstract":"<div><p>Since it has been proposed that oxygen radical inactivation of key enzymes plays a critical role in cell aging, we have investigated the effects of a thiolic free radical scavenger on the oxidative phosphorylation enzymes of liver mitochondria from female OF-1 mice. At 48 weeks of age a control group was fed standard food pellets and another group received pellets containing 0.3% (w/w) of <em>N</em>-acetylcysteine. A 24-week treatment resulted in a significant increase in the specific activities of complex I, IV and V in the hepatic mitochondria of the <em>N</em>-acetylcysteine-treated animals as compared to aged controls.</p></div>","PeriodicalId":100501,"journal":{"name":"European Journal of Pharmacology: Environmental Toxicology and Pharmacology","volume":"292 3","pages":"Pages 333-335"},"PeriodicalIF":0.0,"publicationDate":"1995-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0926-6917(95)90041-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18796287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antagonism by paraquat of the relaxing effects of acetylcholine and A23187 in rat thoracic aorta","authors":"Kuei-Sen Hsu,&nbsp;Shoei-Yn Lin-Shiau","doi":"10.1016/0926-6917(95)90038-1","DOIUrl":"10.1016/0926-6917(95)90038-1","url":null,"abstract":"<div><p>Paraquat, a widely used herbicide, has been reported to be capable of producing superoxide. In the present paper, therefore, the possibility of paraquat inhibiting endothelium-dependent relaxation, mediated by the production of nitric oxide, was tested. The relaxing effects of acetylcholine and A23187, but not that of sodium nitroprusside, in the rat thoracic aorta were found to be inhibited by paraquat in a concentration-dependent manner. In contrast, paraquat was totally inactive with regard to the aortic contractions induced by either norepinephrine or prostaglandin F_2α. The inhibitory action of paraquat could be antagonized by superoxide dismutase but not by catalase and indomethacin. All of these findings indicate that superoxide anions produced by paraquat in the endothelium contribute to a decrease in the relaxation response to acetylcholine and A23187 by interfering with endothelium-derived nitric oxide.</p></div>","PeriodicalId":100501,"journal":{"name":"European Journal of Pharmacology: Environmental Toxicology and Pharmacology","volume":"292 3","pages":"Pages 315-320"},"PeriodicalIF":0.0,"publicationDate":"1995-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0926-6917(95)90038-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18796285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}