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  • 1
    ISSN: 1474-8673
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Chemistry and Pharmacology , Medicine
    Notes: 1 In the present investigation we examined the regulation of calmodulin (CaM)- and protein kinase C (PKC)-dependent pathways by cytosolic Ca2+ in the contraction of cat lower oesophageal sphincter (LES). 2 Force developed in response to increasing doses of acetylcholine (ACh) was directly related to the increase of the [Ca2+]i measured by fura-2. Thapsigargin, which depletes Ca2+ stores, reduced the contraction and the [Ca2+]i. In addition, contraction in response to maximal ACh was reduced by the CaM inhibitor CGS9343B but not by the PKC inhibitor chelerythrine. The contraction in response to submaximal ACh was reduced by chelerythrine but not by CGS9343B. 3 In permeabilized cells, the contraction in response to low Ca2+ (0.54 μm) was also reduced by CGS9343B. 4 The response to high Ca2+ (1.0 μm) was reduced by CGS9343B. ACh also inhibited PKC activation induced by diacylglycerol, which activation is inhibited by the N-myristoylated peptide inhibitor derived from pseudosubstrate sequences of PKCαβγ (myr-PKC-αβγ), but not of myr-PKC-α. 5 These data are consistent with the view that activated CaM-dependent pathways inhibit PKC-dependent pathways, this switch mechanism might be regulated by Ca2+ in the LES.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Autonomic & autacoid pharmacology 22 (2002), S. 0 
    ISSN: 1474-8673
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Chemistry and Pharmacology , Medicine
    Notes: 1 This study was aimed at evaluating the effect of rutin and harmaline (1-methyl-7-methoxy-3,4-dihydro-β-carboline) on the development of the surgically induced reflux oesophagitis, on gastric secretion, lipid peroxidation, polymorphonucleocytes (PMNs) accumulation, superoxide and hydroxyl radical production in PMNs, cytokine [interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α)] production in blood and [Ca2+]i mobilization in PMNs. 2 Rutin and harmaline significantly prevented the development of reflux oesophagitis and gastric secretion. Treatments of oesophagitis rats with rutin and harmaline inhibited lipid peroxidation, and myeloperoxidase (MPO) in the oesophagus in comparison with untreated rats. 3 Superoxide anion and hydrogen peroxide production in 1 μm formylmethionylleucylphenylalanine (fMLP)- or 0.1 μg ml−1N-phorbol 12-myristate 13-acetate (PMA)-activated PMNs was inhibited by rutin and harmaline in a dose-dependent fashion. Rutin and harmaline effectively scavenged the hydroxyl radical and hydrogen peroxide. Treatments of oesophagitis rats with rutin and harmaline inhibited IL-1β production in the oesophagus in comparison with untreated rats, but TNF-α production was not affected by rutin and harmaline. The fMLP-induced elevation of [Ca2+]i was inhibited by rutin. 4 The results of this study suggest that rutin and harmaline may have beneficial protective effects against reflux oesophagitis by the inhibition of gastric acid secretion, oxidative stress, inflammatory cytokine production (i.e. IL-1β), and intracellular calcium mobilization in PMNs in rats.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1474-8673
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Chemistry and Pharmacology , Medicine
    Notes: 1 This study evaluated the inhibitory action of apigenin-7-O-β-d-glucuronopyranoside (AGC), apigenin, and omeprazole on reflux oesophagitis and gastritis in rats. AGC was isolated from Clerodendron trichotomum leaves. 2 Oesophagitis and gastritis were induced by surgical procedure and the administration of indomethacin, respectively. The intraduodenal (i.d.) administration of AGC decreased the volume of gastric juice and increased the gastric pH compared with apigenin and omeprazole. The acid output was more inhibited by AGC in a dose-dependent manner than by apigenin and omeprazole. Compared with apigenin and omeprazole, AGC significantly decreased the size of gastric lesions, which were induced by exposure of the gastric mucosa to indomethacin. 3 Malondialdehyde (MDA) content, which is the end product of lipid peroxidation, was increased significantly after the induction of reflux oesophagitis. The MDA content was decreased by AGC (i.d. 3 mg kg−1), but not by either apigenin or omeprazole. This suggests that AGC has an antioxidative effect. In the oesophagitis group, the mucosal levels of glutathione (GSH) were significantly lower than that in the normal group. However, the GSH levels were preserved after administering the AGC, suggesting that AGC possesses scavenging activity. 4 In summary, AGC is more potent than apigenin and omeprazole at inhibiting reflux oesophagitis and gastritis and may therefore be a promising drug for their treatment.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Autonomic & autacoid pharmacology 25 (2005), S. 0 
    ISSN: 1474-8673
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Chemistry and Pharmacology , Medicine
    Notes: 1 We examined whether extremely low frequency electromagnetic fields (ELF-EMF) affect the basal level of cardiovascular parameters and influence of drugs acting on the sympathetic nervous system. 2 Male rats were exposed to sham control and EMF (60 Hz, 20 G) for 1 (MF-1) or 5 days (MF-5). We evaluated the alterations of blood pressure (BP), pulse pressure (PP), heart rate (HR), and the PR interval, QRS interval and QT interval on the electrocardiogram and dysrhythmic ratio in basal level and dysrhythmia induced by β-adrenoceptor agonists. 3 In terms of the basal levels, there were no statistically significant differences among control, MF-1 and MF-5 in PR interval, QRS interval, mean BP, HR and PP. However, the QT interval, representing ventricular repolarization, was significantly reduced by MF-1 (P 〈 0.05). 4 (−)-Dobutamine (β1-adrenoceptor-selective agonist)-induced tachycardia was significantly suppressed by ELF-EMF exposure in MF-1 for the increase in HR (ΔHR), the decrease in QRS interval (ΔQRS) and the decrease in QT (ΔQT) interval. Adrenaline (nonselective β-receptor agonist)-induced dysrhythmia was also significantly suppressed by ELF-EMF in MF-1 for the number of missing beats, the dysrhythmic ratio, and the increase in BP and PP. 5 These results indicated that 1-day exposure to ELF-EMF (60 Hz, 20 G) could suppress the increase in HR by affecting ventricular repolarization and may have a down-regulatory effect on responses of the cardiovascular system induced by sympathetic agonists.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Autonomic & autacoid pharmacology 23 (2003), S. 0 
    ISSN: 1474-8673
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Chemistry and Pharmacology , Medicine
    Notes: 1 We examined the role of the NO/cyclic GMP (cyclic GMP) pathway in nitric oxide (NO)- and vasoactive intestinal peptide (VIP)-induced relaxation of feline lower oesophageal sphincter (LES). Furthermore, it was studied whether methylene blue, LY83583 and ODQ, which are soluble guanylate cyclase (sGC) inhibitors, could inhibit NO-induced relaxation.2 The nitric oxide synthase (NOS) inhibitor, N-nitro-l-arginine (l-NNA) had no effect in sodium nitropruside (SNP)-induced relaxation, but 3-morpholinosydnonimine-N-ethylcarbamide (SIN-1)-induced relaxation was decreased by the pretreatment of l-NNA, which showed that SIN-1, not SNP, could activate NOS to cause relaxation. Methylene blue and LY83583 did not inhibit the relaxation by SNP and SIN-1. However, the more specific sGC inhibitor ODQ blocked the relaxation induced by NO donors.3 To identify the relationship of NOS, sGC and adenylate cyclase in VIP-induced relaxation, tissue were pretreated with l-NNA and ODQ and SQ22536. These inhibitors produced significant inhibition of this response to VIP. The adenylyl cyclase inhibitor SQ 22536 also inhibited relaxation by VIP.4 In conclusion, our data showed that SNP- and SIN-1-induced relaxation was mediated by sGC. Of sGC inhibitors, methylene blue and LY83583 were not adequate for the examination of NO donor-induced feline LES smooth muscle relaxation. VIP also caused relaxation by the pathway involving NO and cGMP and cAMP.
    Type of Medium: Electronic Resource
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