bluuebunny/crossref_metadata_2025_split huggingface dataset:
Species differences in bradykinin receptor‐mediated responses of the airways
Authors: Ellis K. M. , Fozard J. R. 
Published: March 2003

Summary 1 Bradykinin (BK) is a nine amino acid peptide (Arg‐Pro‐Pro‐Gly‐Phe‐Ser‐Pro‐Phe‐Arg) formed from the plasma precursor kininogen during inflammation and tissue injury. The actions of BK are mediated by G protein‐coupled cell surface receptors, designated B1 and B2. 2 BK has a plethora of effects in the airways including bronchoconstriction, bronchodilation, stimulation of cholinergic and sensory nerves, mucus secretion, cough and oedema resulting from promotion of microvascular leakage. These airway effects are mediated in the main by the B2 receptor subtype. 3 BK acts mainly indirectly, primarily through airway nerve activation, but also by the release of prostanoids, thromboxanes and nitric oxide (NO). 4 Airway responses to BK have been studied in detail in guinea‐pigs, mice, sheep and rats. This review describes the effects of BK in these species and draws comparison with its effects in normal humans and patients with respiratory diseases. 5 Despite its many and varied effects in the airways of animals and man, the exact contribution of BK to airways disease remains unclear.
Dual adrenergic control of in vivo choline levels in the mouse major salivary glands
Authors: Murai S. , Saito H. , Shirato R. , Kawaguchi T. 
Published: March 2003

Summary 1 The purpose of this study was to demonstrate that the adrenergic nervous system regulates the in vivo choline levels in the mouse major salivary glands. 2 Methoxamine (α1‐adrenoceptor agonist, 2.5–20 mg kg−1, s.c.) elevated choline levels dose‐dependently and the effect of methoxamine (10 mg kg−1) was completely inhibited by the α‐adrenoceptor antagonist phentolamine (5 mg kg−1, i.p.) but not by the β‐adrenoceptor antagonist propranolol (3 mg kg−1, i.p.). 3 In contrast, isoprenaline (β‐adrenoceptor agonist 0.25–20 mg kg−1, s.c.) lowered choline levels and the effect of isoprenaline (2 mg kg−1) was inhibited by propranolol, but not by phentolamine. 4 Noradrenaline (1–4 mg kg−1, s.c.) manifested both the α‐ and β‐adrenergic actions depending on its dose. Noradrenaline at 1–2 mg kg−1, lowered choline levels and the effect of noradrenaline (1 mg kg−1) was inhibited by propranolol, but not by phentolamine. On the other hand, noradrenaline (4 mg kg−1) elevated choline levels and the effect was blocked by phentolamine, but not by propranolol. 5 Tyramine (5–80 mg kg−1, s.c.) elicited the release of noradrenaline from sympathetic nerve terminals and induced essentially the same effects on the choline levels as noradrenaline. Tyramine (10 mg kg−1) lowered choline levels and the effect was inhibited by propranolol, but not by phentolamine. However, tyramine (80 mg kg−1) elevated choline levels and the effect was inhibited by phentolamine, but not by propranolol. 6 These results suggest that choline levels in the salivary glands may be under separate α‐ and β‐adrenergic control and suggest a possibility that the neurotransmitter noradrenaline released for sympathetic nerve terminals can manage the dual control of choline levels in some autonomic organs in a characteristic dose‐dependent manner.
Effects of defibrotide, a novel oligodeoxyribonucleotide, on ischaemia and reperfusion injury of the rat liver
Authors: Kim Kwang Joon , Shin Yong Kyoo , Song Jin Ho , Oh Byung Kwon , Choi Myung Sup , Sohn Uy Dong 
Published: March 2003

Summary 1 The purpose of this study was to investigate the protective effects of defibrotide, a single‐stranded polydeoxyribonucleotide, on ischaemia–reperfusion injury to the liver using a rat model. 2 Ischaemia of the left and median lobes was created by total inflow occlusion for 30 min followed by 60 min of reperfusion. Hepatic injury was assessed by the release of liver enzymes (alanine transferase, ALT and lactic dehydrogenase, LDH). Hepatic oxidant stress was measured by superoxide production, lipid peroxidation and nitrite/nitrate formation. Leukocyte–endothelium interaction and Kupffer cell mobilization were quantified by measuring hepatic myeloperoxidase (MPO), polymorphonuclear leukocyte adherence to superior mesenteric artery (SMA) and immunostaining of Kupffer cell. 3 Defibrotide treatment resulted in a significant inhibition of postreperfusion superoxide generation, lipid peroxidation, serum ALT activity, serum LDH activity, MPO activity, serum nitrite/nitrate level, leukocyte adherence to SMA, and Kupffer cell mobilization, indicating a significant attenuation of hepatic dysfunction. 4 A significant correlation existed between liver ischaemia/reperfusion and hepatic injury, suggesting that liver ischaemia/reperfusion injury is mediated predominantly by generation of oxygen free radicals and mobilization of Kupffer cells. 5 We conclude that defibrotide significantly protects the liver against liver ischaemia/reperfusion injury by interfering with Kupffer cell mobilization and formation of oxygen free radicals. This study provides strong evidence that defibrotide has important beneficial effects on acute inflammatory tissue injury such as that occurring in the reperfusion of the ischaemic liver.
Effects of rutin and harmaline on rat reflux oesophagitis
Authors: Shin Y. K. , Sohn U. D. , Choi M. S. , Kum C. , Sim S. S. , Lee M. Y. 
Published: March 2003

Summary 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.
Induction of duodenal motility activates the sphincter of Oddi (SO)‐duodenal reflex in the Australian possum in vitro
Authors: Konomi H. , Simula M. E. , Meedeniya A. C. B. , Toouli J. , Saccone G. T. P. 
Published: March 2003

Summary 1 The aim of this study was to determine if stimulation of duodenal motility by duodenal fluid distension or by administration of carbachol, activates the sphincter of Oddi‐duodenal reflex, in an in vitro preparation from the Australian possum. 2 Duodenal distension was achieved by infusion of Krebs solution (0–8 cm H2O). In separate experiments, the sphincter of Oddi (SO) was partitioned from the duodenum and carbachol (10−7−5 × 10−6 m) added to the duodenal compartment. 3 Fluid distension increased duodenal motility to 120–600% of control activity. These treatments induced increased SO motility (to 120–390% of control) in six preparations, reduced activity (to 60% of control) in one and no response in another. 4 Addition of carbachol to the duodenal compartment resulted in increased duodenal motility. SO motility was increased in seven preparations, reduced in another two and no response were evoked in two others. All SO responses were blocked by tetrodotoxin pretreatment. 5 These data suggest that the SO receives inputs from duodenal mechano and/or stretch receptors resulting in excitatory or inhibitory responses, with the excitatory response dominating. These findings support the role for the SO‐duodenal reflex in preventing duodeno‐biliary/pancreatic reflux during periods of elevated duodenal activity.
Functional importance of the actin cytoskeleton in contraction of bovine iris sphincter muscle
Authors: Filipe J. A. C. , Nunes J. P. L. 
Published: March 2003

Summary 1 The contractile capacity of smooth muscle cells depends on the cytoskeletal framework of the cell. The aim of this study was to determine the functional importance of both the actin and the tubulin components of the cytoskeleton in contractile responses of the bovine isolated iris sphincter muscle. 2 In each preparation, two contractions to the muscarinic agonist carbachol were obtained. The maximum responses of the first contractions were taken as 100%. The second contractions to carbachol were elicited in the presence of either cytochalasin B (50 and 5 μm), an inhibitor of the actin cytoskeleton, or colchicine (100 μm), an inhibitor of the tubulin cytoskeleton (30 min incubation). 3 Cytochalasin B, at a concentration of 50 μm, significantly decreased the contractions induced by carbachol, with the maximum response reduced to 21.8 ± 6.6% (n = 12) of the initial maximum. The maximal contractions to carbachol in the presence of colchicine reached 96.2 ± 7.9% (n = 9) of the initial contraction, which was not significantly different from control second responses to carbachol with neither drug present, which reached 113.3 ± 7.6% (n = 7). 4 The effect of cytochalasin B was dose‐dependent, since at a lower concentration of 5 μm, the drug decreased the maximum contraction to carbachol to 60.3 ± 8.8% (n = 6). The effect of cytochalasin B was at least partially reversible, since after the use of the higher concentration of 50 μm, contractions to carbachol increased to 62.3 ± 15.5% (n = 4) of the maximal response, after 1 h repeated washing of the preparations. 5 Cytochalasin D, at a concentration of 50 μm, completely abolished the contractions induced by carbachol (n = 4). 6 These findings suggest that in bovine iris sphincter muscle, contractions to carbachol are highly dependent, from a functional point of view, on actin polymerization, and not, to any important degree, on the polymerization of tubulin.
Studies on the mechanism of enhancement of purinergic transmission by caffeine in the guinea‐pig isolated vas deferens
Authors: Ziogas J. , O'Farrell M. 
Published: March 2003

Summary 1 Purinergic transmission from sympathetic nerves in the guinea‐pig vas deferens was monitored using intracellular recording techniques. Stimulation of the hypogastric nerve with trains of 15 pulses at 1 Hz evoked excitatory junction potentials (EJPs) which increased in amplitude from the first pulse and reached a maximum after 6–8 pulses. 2 Caffeine (3 and 10 mm), depolarized cells by 5–10 mV and increased the amplitude of the first few EJPs in each train but reduced the maximum amplitude of EJPs late in the train. 3 The adenosine receptor antagonist 8‐p‐sulphophenyl‐theophylline (8‐SPT; 30 μm) had no effect on either the resting membrane potential or the EJP amplitude; however, at 100 μm it reduced the amplitude of all EJPs by 5–10%. 4 Adenosine (10 and 30 μm) reduced the amplitude of EJPs in a concentration‐dependent manner. The inhibitory effect of adenosine on EJP amplitude was prevented by pretreatment with either caffeine (3 mm) or 8‐SPT (30 μm). 5 Ryanodine (30 μm) did not alter EJP amplitude and did not inhibit the enhancement of the first EJP by caffeine (3 mm). Incubation of the tissue with the cell permeable calcium chelator 1‐2‐bis(o‐aminophenoxy)ethane‐N,N‐N′,N′‐tetraacetic acid (BAPT‐AM) resulted in a depression of EJP amplitude and a longer time to reach maximum amplitude. In cells that had been exposed to BAPT‐AM, caffeine 3 mm still increased amplitude of EJP early in the train. 6 The phosphodiesterase inhibitor, 3‐isobutyl‐1‐methylxanthine (IBMX; 500 μm), hyperpolarized cells and increased the amplitude of EJP throughout the train of stimulation. In the presence of IBMX, caffeine 3 mm still depolarized the cells and enhanced the EJP early in the train of stimulation. 7 The findings in this study confirm that caffeine and 8‐SPT are effective inhibitors of the actions of adenosine. However, caffeine has an additional action to enhance EJP early during a train of stimulation, which cannot be attributed to blockade of adenosine receptors, but which may be related to inhibition of phosphodiesterase.
Modulatory effect of the adrenergic system upon fibroblast proliferation: participation of β3‐adrenoceptors
Authors: Anesini C. , Borda E. 
Published: March 2003

Summary 1 The β3‐adrenoceptor agonist ZD 7114, like the non‐selective β‐adrenoceptor agonist isoprenaline, but unlike the β1‐adrenoceptor agonist dobutamine and the β2‐adrenoceptor agonist salbutamol, produced an increment on mouse embryonic fibroblast proliferation. The half‐maximal stimulation of cell growth occurred at substantially lower concentrations with the β3‐adrenoceptor agonist (EC50: 5.5 × 10−8 m) than with isoprenaline (EC50: 1.25 × 10−6 m). 2 The selective β3‐adrenoceptor antagonist SR 5923 OA prevented the β3‐stimulated fibroblast proliferation. Conversely, practolol and butoxamine did not prevent fibroblast growth. 3 Additionally, a decrease of cAMP was obtained in fibroblasts cells upon stimulation with isoprenaline and ZD 7114. 4 The expression of β‐adrenoreceptors on fibroblast cells was also studied by radioligand binding. The Ki values in the presence of β1‐ and β2‐adrenoceptor antagonist was two‐fold higher than the Ki values for β3 adrenoceptor antagonist indicating the presence of A3‐receptor subtype. 5 Inhibitors of different intracellular coupling pathways including phospholipase C (U 73122), protein kinase C (staurosporine), calcium/calmodulin (trifluoroperazine) and calcium channel (verapamil), prevented the stimulatory actions of the selective β3‐adrenoceptor agonist ZD 7114. 6 The presence of β3‐adrenoceptors on embryonic mouse fibroblast cells may play a role in the modulation of cell growth and biologic activity. The mechanism by which ZD 7114 triggers cell proliferation and function, involves the activation of phospholipase C, PKC, calcium/calmodulin and the influx of calcium.
Involvement of κ‐opioid receptors in peripheral response to nerve stimulation in κ‐opioid receptor knockout mice
Authors: Mitolo‐Chieppa D. , Natale L. , Marasciulo F. L. , De Salvatore G. , Mitolo C. I. , Siro‐Brigiani G. , Renna G. , De Salvia M. A. 
Published: March 2003

Summary 1 The present study aimed to evaluate the role of κ‐opioid receptors at two peripheral sites, the vas deferens and the proximal colon, in κ‐opioid receptor knockout mice. We investigated the role of the κ‐opioid receptor in the vas deferens twitch response and in the colonic ‘off‐contraction’, a rebound contractile response which follows the inhibitory response to low frequencies stimulation (10, 20, 30 Hz) and which has been suggested to ‘locally’ reproduce the contractile component of the peristaltic reflex. 2 Transmural stimulation of the vas deferens at lower frequencies (10 Hz, 10 V, 1 ms pulse trains lasting 0.5 s) evoked a contractile response that was significantly higher in the preparations from knockout mice because of lack of κ‐opioid receptors than in wild type mice. A selective κ‐opioid receptor agonist, U‐50,488H, induced a dose‐dependent inhibition of the electrically stimulated contraction in vas deferens. The percentages of reduction of the twitch response were significantly lower in knockout mice than in wild type mice after treatment with U‐50,488H. The reduction of twitch response caused by U‐50,488H was not reversed by administration of nor‐binaltorphimine (nor‐BNI) (5 × 10−6 m), a selective κ‐opioid receptor antagonist, in preparations from both knockout mice and wild type mice. U‐50,488H has no effect on postsynaptic adrenergic receptors, as its administration did not affect the direct contractile response to noradrenaline. 3 Transmural stimulation (5 Hz, 20 V, 2 ms pulse trains lasting 30 s) induced inhibition of spontaneous activity of colonic strips during the period of stimulation, followed by an ‘off‐contraction’ after the cessation of stimulation. The statistical evaluation of the ‘off‐contraction’ responses between the two strains showed no significant difference. The off‐contraction, measured in specimens from knockout mice, was inhibited concentration‐dependently by U‐50,488H (P < 0.01) and significantly less than from wild type mice. 4 The effect of U‐50,488H was not reversed by administration of nor‐BNI (5 × 10−6 m), either in preparations from knockout mice or from wild type mice. 5 Our data may suggest that κ‐opioid receptors are involved in some peripheral responses to the nerve stimulation, as indicated by the effect of U‐50,488H, a selective κ‐opioid receptor agonist. However, the involvement of κ‐opioid receptor was also present, although less apparent, in κ ‐opioid receptor knockout mice, suggesting either that this drug acts not only on κ‐opioid receptors but also on other receptor sites, such as κ‐like receptors. An alternative interpretation can be related to a sodium channel blocking action of U‐50,488H, which could explain the inhibitory effects of twitch response still present but less evident in knockout strain and the lack of effect of the antagonist nor‐BNI.
Comparison of catecholamine release in the isolated adrenal glands of SHR and WKY rats
Authors: Lim D.‐Y. , Jang S.‐J. , Park D.‐G. 
Published: March 2003

Summary 1 The present study was designed to investigate the secretion of catecholamines (CA) evoked by stimulation of cholinergic receptors and membrane depolarization from the isolated perfused adrenal gland of spontaneously hypertensive rats (SHR) and normotensive Wistar–Kyoto rats (WKYR) at adult age. 2 The wet weight of adrenal gland in SHR was greater than that in WKYR. The CA releasing responses evoked by acetylcholine (5.32 × 10−3 m), and high potassium (5.6 × 10−2 m), a membrane depolarizer, were significantly lower in WKYR than in SHR. 3 The secretory responses of CA evoked by DMPP (10−4 m for 2 min), a selective agonist of neuronal nicotinic receptors, and McN‐A‐343 (10−4 m for 2 min), a selective agonist of neuronal muscarinic receptors, were also significantly lower in WKYR than in SHR. 4 The CA release evoked by Bay‐K‐8644 (10−5 m), a dihydropyridine‐sensitive Ca2+ channel activator, and cyclopiazonic acid (10−5 m), a selective inhibitor of Ca2+‐ATPase in the endoplasmic reticulum, were also significantly greater in SHR than WKYR. 5 Taken together, these experimental results demonstrate that the CA secretion evoked by stimulation of cholinergic (nicotinic and muscarinic) receptors as well as membrane depolarization is enhanced more greatly in the perfused adrenal glands of SHR than in those of WKYR. It is suggested that the augmented CA release in SHR compared with WKYR was involved in essential hypertensive pathogenesis.
Ironing out Parkinson's disease: is therapeutic treatment with iron chelators a real possibility?
Authors: Kaur Deepinder , Andersen Julie K. 
Published: March 2003

SummaryLevels of iron are increased in the brains of Parkinson's disease (PD) patients compared to age‐matched controls. This has been postulated to contribute to progression of the disease via several mechanisms including exacerbation of oxidative stress, initiation of inflammatory responses and triggering of Lewy body formation. In this minireview, we examine the putative role of iron in PD and its pharmacological chelation as a prospective therapeutic for the disease.
Asymmetry of DNA replication fork progression in Werner's syndrome
Authors: Rodríguez‐López Ana M. , Jackson Dean A. , Iborra Francisco , Cox Lynne S. 
Published: March 2003

SummaryHuman aging is associated with accumulation of cells that have undergone replicative senescence. The rare premature aging Werner's syndrome (WS) provides a phenocopy of normal human aging and WS patient cells recapitulate the aging phenotype in culture as they rapidly lose the ability to proliferate or replicate their DNA. WS is associated with loss of functional WRN protein. Although the biochemical properties of WRN protein, which possesses both helicase and exonuclease activities, suggest an involvement in DNA metabolism, its action in cells is not clear. Here, we provide experimental evidence for a role of the WRN protein in DNA replication in normally proliferating cells. Most importantly, we demonstrate that in the absence of functional WRN protein, replication forks from origins of bidirectional replication fail to progress normally, resulting in marked asymmetry of bidirectional forks. We propose that WRN acts in normal DNA replication to prevent collapse of replication forks or to resolve DNA junctions at stalled replication forks, and that loss of this capacity may be a contributory factor in premature aging.
Interpreting interactions between treatments that slow aging
Authors: Gems David , Pletcher Scott , Partridge Linda 
Published: March 2003

SummaryA major challenge in current research into aging using model organisms is to establish whether different treatments resulting in slowed aging involve common or distinct mechanisms. Such treatments include gene mutation, dietary restriction (DR), and manipulation of reproduction, gonadal signals and temperature. The principal method used to determine whether these treatments act through common mechanisms is to compare the magnitude of the effect on aging of each treatment separately with that when two are applied simultaneously. In this discussion we identify five types of methodological shortcomings that have marred such studies. These are (1) submaximal lifespan‐extension by individual treatments, e.g. as a result of the use of hypomorphic rather than null alleles; (2) effects of a single treatment on survival through more than one mechanism, e.g. pleiotropic effects of lifespan mutants; (3) the difficulty of interpreting the magnitude of increases in lifespan in double treatments, and failure to measure and model age‐specific mortality rates; (4) the non‐specific effects of life extension suppressors; and (5) the possible occurrence of artefactual mutant interactions. When considered in the light of these problems, the conclusions of a number of recent lifespan interaction studies appear questionable. We suggest six rules for avoiding the pitfalls that can beset interaction studies.