bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neurochemical regulation of cough response to capsaicin in guinea‐pigs
Authors: Li J. Q. , Jia Y. X. , Yamaya M. , Arai H. , Ohrui T. , Sekizawa K. , Sasaki H. 
Published: March 2003

Summary 1 Although monumental efforts have been made to define the action sites of cough, the importance of neurotransmitter systems in the cough reflex has received limited attention. We studied the roles for four major neurotransmitters [acetylcholine, histamine, serotonin (5‐hydroxytryptamine, 5‐HT) and dopamine] in the modulation of the cough reflex. 2 Atropine (muscarinic cholinergic blocking agent), pyrilamine maleate (PM, histamine H1 blocker), cimetidine (histamine H2 blocker), 8‐hydroxy‐2‐(di‐n‐propylamino)‐tetralin (8‐OH‐DPAT, specific 5‐HT1A receptor agonist) and SCH‐23390 (selective dopamine D1 receptor antagonist) were examined on the cough response to inhaled capsaicin in conscious guinea‐pigs. 3 All the drugs significantly decreased the number of capsaicin‐induced coughs in a dose‐dependent manner. To compare the sensitivity of these drugs on cough response, we calculated the effective doses for 50% inhibition of cough (ED50) when the animals were exposed to 3 × 10−4 m capsaicin. The ED50 values were 0.03 μm kg−1 for atropine, 0.2 μm kg−1 for 8‐OH‐DPAT, 6.2 μm kg−1 for SCH‐23390, 8.5 μm kg−1 for PM and 13.9 μm kg−1 for cimetidine. 4 These findings indicated that all these four neurotransmitters may be involved in the regulation of the cough reflex. Multiple changes of these neurotransmitters in disorders of the central nervous system might synergically affect the cough reflex.
Salivary glands and noradrenergic transmission in diabetic rats
Authors: Vatta M. S. , Hope S. I. , Prendes G. M. , Bianciotti L. G. , Elverdin J. C. , Fernandez B. E. 
Published: March 2003

Summary 1 Type 2 diabetes is associated with diverse oral pathologies in which salivary flow reduction is one of the causes of these oral abnormalities. Scarce literature exists regarding noradrenergic transmission and adrenergic‐induced salivary flow in submaxillary and parotid glands of type 2 diabetic rats. 2 We studied noradrenergic transmission as well as the secretory response to α1‐ and β‐adrenoceptor stimulation in the parotid and submaxillary glands of type 2 diabetic rats. 3 Diabetic rats exhibited diminished neuronal uptake, release and endogenous content of noradrenaline (NE) in both salivary glands. Further, NE synthesis was also diminished accompanied by decreased tyrosine hydroxylase activity. Salivary flow responses to α1‐(methoxamine) and β‐(isoprenaline) adrenoceptor stimulation were reduced in the submaxillary as well as the parotid glands of diabetic rats. 4 Our results suggest that the reduction of noradrenergic transmission in the salivary glands of type 2 diabetic rats is in part responsible for the diminished salivary flow evoked by α1‐ and β‐adrenergic stimulation. Reduced noradrenergic activity may contribute to the pathophysiology of oral abnormalities in diabetic patients.
The enhanced plasma levels of soluble tumor necrosis factor receptors (sTNF‐R1; sTNF‐R2) and interleukin‐10 (IL‐10) in patients suffering from chronic heart failure are reversed in patients treated with β‐adrenoceptor antagonist
Authors: Loppnow Harald , Werdan Karl , Werner Claudia 
Published: March 2003

Summary 1 Cytokines may parallel or regulate the beneficial effects of β‐adrenoceptor antagonist treatment observed in chronic heart failure (CHF) patients. Therefore, this study was performed in order to investigate alterations of cytokine levels in β‐blocker‐treated patients suffering from CHF. 2 We investigated plasma cytokine levels in eight healthy controls and 12 CHF patients. The patients were treated with standard medication (CHFstd) or with standard medication and additional β1‐blocker metoprolol (CHFmet). Interleukin‐(IL)‐1α, IL‐1β, IL‐1 receptor antagonist (IL‐1ra), IL‐2, IL‐6, IL‐8, IL‐10, tumor necrosis factor‐α (TNF), soluble TNF receptor type 1 (sTNF‐R1), sTNF‐R2, and sCD14 were measured by ELISA. 3 IL‐1α and IL‐1β were not detectable in any of the tested groups. IL‐2, TNF, or sCD14 were not altered as compared with healthy control subjects. CHFstd patients expressed enhanced IL‐1ra, IL‐6, IL‐8, IL‐10, sTNF‐R1 and sTNF‐R2. In CHFmet patients IL‐1ra, IL‐6 and IL‐8 remained at the same level. In contrast, sTNF‐R1 levels were significantly reduced, although not to control, whereas the sTNF‐R2 and IL‐10 were reduced to control levels. 4 The cAMP levels of mononuclear cells – recalculated for the patients included in this study from previous work [Werner et al. (2001). Basic Res. Cardiol., 96, 290]– correlated inversely with the sTNF‐R2 data (Pearson, r=−0.46; P=0.041; Spearman, r=−0.64, P=0.002). 5 The present data indicate an interaction of the neurohumoral and the cytokine system in CHF patients at the cAMP level. Thus, measurement and correlation of sTNF‐R2 and cAMP may provide a tool useful during investigation of β‐blocker therapy.
The effect of nitric oxide synthase blockade on responses to morphine in rat aortic rings
Authors: Ahin N. , Özdem S. , Adan G. 
Published: March 2003

Summary 1 It has been suggested that opioids may play an indirect role in the regulation of the peripheral circulation through the control of nitric oxide (NO) release in vascular tissue. The current study was undertaken to investigate the effect of nitric oxide synthase (NOS) blockade on responses to morphine in phenylephrine (PE)‐ or KCl‐precontracted rat aortic rings. 2 Morphine (3 × 10−8−3 × 10−5 m) administration did not cause any significant effect on basal tonus of endothelium‐intact or endothelium‐denuded preparations. Morphine produced concentration‐dependent relaxation responses in endothelium‐intact as well as in endothelium‐denuded rat aortic rings precontracted by PE or KCl. Removal of endothelium did not significantly alter the relaxation responses to morphine. 3 The relaxant responses to morphine were significantly and partially inhibited by pretreatment of tissues with naloxone (NAL, 3 × 10−5 m) for 5 min. The inhibitory effect of NAL on relaxant responses to morphine in PE‐ or KCl‐precontracted rings did not differ significantly between endothelium‐intact and endothelium‐denuded preparations. 4 Incubation of endothelium‐intact or endothelium‐denuded rat aortic rings with NOS inhibitor, Nω‐nitro‐l‐arginine methyl ester (l‐NAME, 10−4 m) for 20 min did not cause a significant inhibition on relaxation responses to morphine. 5 These findings confirmed the presence of opiate receptors in rat thoracic aorta, but suggested that mechanisms other than NO release play a role in the relaxant effect of morphine on rat aortic rings.
Neuropeptide Y inhibits double peaked vasoconstrictor responses to periarterial nerve stimulation primarily through prejunctional Y2 receptor subtype in canine splenic arteries
Authors: Yang X.‐P. , Chiba S. 
Published: March 2003

Summary 1 The effects of BIIE 0246, a novel and non‐peptide neuropeptide Y (NPY) Y2 receptor antagonist on sympathetic vasoconstriction of the canine splenic artery were investigated. 2 The vasoconstrictor response to periarterial electrical nerve stimulation was described to be a double peaked vasoconstriction consisting of an initial transient, dominantly P2X purinoceptor‐mediated constriction followed by a prolonged, mainly α1 adrenoceptor‐induced response. 3 BIIE 0246 at a concentration of 0.1–1 μm dose‐dependently potentiated double peaked constrictions at low frequencies (1 and 4 Hz), whereas at high frequency (10 Hz), it failed to affect these responses. BIIE 0246 (1 μm) also enhanced double peaked responses even in the presence of rauwolscine (0.1 μm). NPY (13–36) (1–100 nm), a selective Y2 receptor agonist reduced these two peaked responses in a dose‐related manner. The vasoconstriction to noradrenaline (0.1–10 nmol) or adenosine triphosphate (0.01–1 μmol) was not significantly influenced by either 1 μm BIIE 0246 or 100 nm NPY (13–36). Exposure of tissues to 1 μm BIIE 0246 almost completely prevented the suppression of double peaked constrictions by NPY (13–36) (10 nm) or by NPY (10 nm). 4 We conclude that NPY inhibits sympathetic purinergic and adrenergic vasoconstrictions through an activation of prejunctional Y2 receptor subtype in the neurovascular junction of the canine splenic artery.
GABAB receptor function in the ileum and urinary bladder of wildtype and GABAB1 subunit null mice
Authors: Sanger G. J. , Munonyara M. L. , Dass N. , Prosser H. , Pangalos M. N. , Parsons M. E. 
Published: March 2003

Summary 1 GABAB1 receptor subunit knockout mice were generated and the effects of the GABAB receptor agonist, baclofen, were evaluated within the peripheral nervous system (PNS) of wildtype (+/+), heterozygote (+/–) and knockout (–/–) animals. For this purpose, neuronally‐mediated responses were evoked in both the isolated ileum and urinary bladder, using selective electrical field stimulation (EFS). 2 In ileum resected from 4–8‐week‐old‐mice, low frequencies of EFS (0.5 Hz) evoked irregular muscle contractions which were prevented by atropine 1 μM and reduced by baclofen (33.4 ± 5.6%, 100 μm). The latter effect was antagonized by the GABAB receptor antagonist CGP54626 0.2 μm. Baclofen 100 μm did not affect contractions of similar amplitude induced by carbachol, indicating that the ability of baclofen to inhibit cholinergic function in mouse ileum may be due to an action at prejunctional GABAB receptors. 3 To avoid the development of grand mal seizure by GABAB1 (–/–) mice, a behaviour observed when the mice were greater than 3 weeks old, it was necessary to study the effects of this knockout in 1–3‐week‐old‐animals. However, at this age, EFS at 0.5 Hz did not evoke robust muscle contractions. Consequently we used EFS at 5 Hz, which did evoke cholinergically mediated contractions, found to be of similar amplitude in (+/+) and (+/–) mice, of both 1–3 weeks and 4–8 weeks of age. At this frequency of EFS, baclofen reduced the amplitude of the evoked contractions [n=6 (+/+) and n=5 (+/–), IC50 19.2 ± 4.8 μm) and this effect was greatly reduced in the presence of CGP54626 0.2 μm. 4 In urinary bladder from 1–3‐week‐old‐mice, using higher frequencies of EFS to evoke clear, nerve‐mediated contractions (10 Hz), baclofen 10–300 μm concentration‐dependently inhibited contractions in (+/+) mice (IC50 9.6 ± 3.8 μm). This effect was inhibited by CGP54626 (0.2 μm, 46.2 ± 13.6% inhibition, 300 μm baclofen n=7) a concentration which, by itself, had no effect on the EFS‐evoked contractions. 5 The effects of baclofen in both ileum and urinary bladder were absent in the GABAB1 receptor subunit (–/–) mice; however, responses to EFS were unaffected in (–/–) when compared to the (+/+) mice. 6 Our data suggest that, as in the central nervous system (CNS), the GABAB1 receptor subunit is an essential requirement for GABAB receptor function in the enteric and PNS. As such, these data do not provide a structural explanation for the existence of putative subtypes of GABAB receptor, suggested by studies such as those in which different rank‐orders of GABAB agonist affinity have been reported in different tissues.
Pharmacological analysis of functional neurovascular transmission in canine splenic arteries: role of neuropeptide Y
Authors: Chiba S. , Yang X.‐P. 
Published: March 2003

Summary1 The effects of neuropeptide Y (NPY) upon the isolated vasculature are reviewed.2 The vasconstrictor responses to periarterial nerve stimulation (PNS) and neurotransmission by noradrenaline (NA) and ATP are discussed and illustrated using canine isolated perfused splenic artery.3 Modulation of the vascular responses to PNS by NPY via pre‐ and post‐junctional NPY Y2and Y1receptors is discussed.4 Evidence is presented for different α1‐adrenoceptor subtypes mediating vasoconstriction to exogenous and endogenously released NA and their different locations in the neurovascular junction and extrajunctional regions.5 Activation of NPY Y1‐receptors potentiates sympathetic nerve activated α1‐adrenoceptor vasoconstriction. The proposal that the postjunctional α1Badrenoceptor may be linked to the NPY Y1‐receptor and is responsible for co‐operation between sympathetic and NPYergic interactions in the vasculature is discussed.
The demography of slow aging in male and female Drosophila mutant for the insulin‐receptor substrate homologue chico
Authors: Tu Meng‐Ping , Epstein Diane , Tatar Marc 
Published: March 2003

SummaryHypomorphic mutants affecting the Drosophila insulin/IGF signal pathway are reported to increase longevity in females but not in males. To understand this sex‐difference, we conducted a large‐scale demographic study with three new isogenic strains of alleles at chico, the insulin‐receptor substrate homologue. We verify that female dwarf homozygotes (ch1/ch1) and normal‐sized heterozygotes (ch1/+) are long‐lived, as originally reported. We find for the first time that male heterozygotes are long‐lived relative to wildtype, by about 50%. The life span of male ch1/ch1 is similar to that of wildtype but these dwarf males age at a slow demographic rate. The levels of demographic frailty and of age‐independent mortality are elevated in ch1/ch1 males, counteracting the effect of slow aging upon life expectancy. Mortality deceleration occurs amongst the oldest‐old wildtype adults, as seen in many organisms. Remarkably, in similarly sized cohorts of male and female ch1/ch1 and of male ch1/+ mortality deceleration is absent. Mortality deceleration is a phenotype of chico.
The shortened replicative life span of prohibitin mutants of yeast appears to be due to defective mitochondrial segregation in old mother cells
Authors: Piper Peter W. , Jones Gary W. , Bringloe David , Harris Nicholas , MacLean Morag , Mollapour Mehdi 
Published: March 2003

SummaryProhibitin proteins have been implicated in cell proliferation, aging, respiratory chain assembly and the maintenance of mitochondrial integrity. The prohibitins of Saccharomyces cerevisiae, Phb1 and Phb2, have strong sequence similarity with their human counterparts prohibitin and BAP37, making yeast a good model organism in which to study prohibitin function. Both yeast and mammalian prohibitins form high‐molecular‐weight complexes (Phb1/2 or prohibitin/BAP37, respectively) in the inner mitochondrial membrane. Expression of prohibitins declines with senescence, both in mammalian fibroblasts and in yeast. With a total loss of prohibitins, the replicative (budding) life span of yeast is reduced, whilst the chronological life span (the survival of stationary cells over time) is relatively unaffected. This effect of prohibitin loss on the replicative life span is still apparent in the absence of an assembled respiratory chain. It also does not reflect the production of extrachromosomal ribosomal DNA circles (ERCs), a genetic instability thought to be a major cause of replicative senescence in yeast. Examination of cells containing a mitochondrially targeted green fluorescent protein indicates this shortened life span is a reflection of defective mitochondrial segregation from the mother to the daughter in the old mother cells of phb mutant strains. Old mother phb mutant cells display highly aberrant mitochondrial morphology and, frequently, a delayed segregation of mitochondria to the daughter. They often arrest growth with their last bud strongly attached and with the mitochondria adjacent to the septum between the mother and the daughter cell.
Life history response of Mediterranean fruit flies to dietary restriction
Authors: Carey James R. , Liedo Pablo , Harshman Lawrence , Zhang Ying , Müller Hans‐Georg , Partridge Linda , Wang Jane‐Ling 
Published: March 2003

SummaryThe purpose of this study was to investigate medfly longevity and reproduction across a broad spectrum of diet restriction using a protocol similar to those applied in most rodent studies. Age‐specific reproduction and age of death were monitored for 1200 adult males and 1200 females, each individually maintained on one of 12 diets fromad libitumto 30% ofad libitum. Diet was provided in a fixed volume of solution that was fully consumed each day, ensuring control of total nutrient consumption for every fly. Contrary to expectation and precedence, increased longevity was not observed at any level of diet restriction. Among females, reproduction continued across all diet levels despite the cost in terms of increased mortality. Among males, life expectancy exceeded that of females at most diet levels. However, in both sexes, mortality increased more sharply and the pattern of survival changed abruptly once the diet level fell to 50% ofad libitumor below, even though the energetic demands of egg production has no obvious counterpart in males. We believe that a more complete picture of the life table response to dietary restriction will emerge when studies are conducted on a wider range of species and include both sexes, more levels of diet, and the opportunity for mating and reproduction.
Assessing metabolic activity in aging Caenorhabditis elegans: concepts and controversies
Authors: Braeckman Bart P. , Houthoofd Koen , Vanfleteren Jacques R. 
Published: March 2003

SummaryIt is widely believed that normal by‐products of oxidative metabolism and the subsequent molecular damage inflicted by them couple the aging process to metabolic rate. Accordingly, high metabolic rates would be expected to accelerate aging, and life‐extending interventions are often assumed to act by attenuating metabolic rate. Notorious examples in Caenorhabditis elegans are food restriction, mutation in the Clock genes and several genes of the insulin‐like signalling pathway. Here we discuss how metabolic rate can be accurately measured and normalized, and how to deal with differences in body size. These issues are illustrated using experimental data of the long‐lived mutant strains clk‐1(e2519) and daf‐2(e1370). Appropriate analysis shows that metabolic rates in wild‐type and in the clk‐1 mutant are very similar. In contrast, the metabolic rate profiles point to a metabolic shift toward enhanced efficiency of oxidative phosphorylation in the daf‐2 worms.
The mitochondrial theory of aging: dead or alive?
Authors: Jacobs Howard T. 
Published: March 2003

AbstractThe mitochondrial theory of aging is based around the idea of a vicious cycle, in which somatic mutation of mtDNA engenders respiratory chain dysfunction, enhancing the production of DNA‐damaging oxygen radicals. In turn, this is proposed to result in the accumulation of further mtDNA mutations. Finally, a bioenergetic crisis leads to overt tissue dysfunction and degeneration. A substantial body of circumstantial evidence seems to support this idea. However, the extent of detectable mtDNA mutation is far less than can easily be reconciled to this hypothesis, unless it is assumed that a subset of cells with much higher than average mtDNA mutation load is systematically lost by apoptosis. A rigorous test of the hypothesis remains to be undertaken, but would require a direct manipulation of the rate of mtDNA mutagenesis, to test whether this could alter the kinetics of aging.
Mitochondrial DNA mutations as a fundamental mechanism in physiological declines associated with aging
Authors: Pak Jeong W. , Herbst Allen , Bua Entela , Gokey Nolan , McKenzie Debbie , Aiken Judd M. 
Published: March 2003

SummaryThe hypothesis that mitochondrial DNA damage accumulates and contributes to aging was proposed decades ago. Only recently have technological advancements, which facilitate microanalysis of single cells or portions of cells, revealed that mtDNA deletion mutations and, perhaps, single nucleotide mutations accumulate to physiologically relevant levels in the tissues of various species with age. Although a link between single nucleotide mutations and physiological consequences in aging tissue has not been established, the accumulation of deletion mutations in skeletal muscle fibres has been associated with sarcopenia. Different, and apparently random, deletion mutations are specific to individual fibres. However, the mtDNA deletion mutation within a phenotypically abnormal region of a fibre is the same, suggesting a selection, amplification and clonal expansion of the initial deletion mutation. mtDNA deletion mutations within a muscle fibre are associated with specific electron transport system abnormalities, muscle fibre atrophy and fibre breakage. These data point to a causal relationship between mitochondrial DNA mutations and the age‐related loss of muscle mass.
Reduced age‐related plasticity of neurotrophin receptor expression in selected sympathetic neurons of the rat
Authors: Cowen T. , Woodhoo A. , Sullivan C. D. , Jolly R. , Crutcher K. A. , Wyatt S. , Michael G. J. , Orike N. , Gatzinsky K. , Thrasivoulou C. 
Published: March 2003

SummarySelective vulnerability of particular groups of neurons is a characteristic of the aging nervous system. We have studied the role of neurotrophin (NT) signalling in this phenomenon using rat sympathetic (SCG) neurons projecting to cerebral blood vessels (CV) and iris which are, respectively, vulnerable to and protected from atrophic changes during old age. RT‐PCR was used to examine NT expression in iris and CV in 3‐ and 24‐month‐old rats. NGF and NT3 expression in iris was substantially higher compared to CV; neither target showed any alterations with age. RT‐PCR for the principal NT receptors, trkA and p75, in SCG showed increased message during early postnatal life. However, during mature adulthood and old age, trkA expression remained stable while p75 declined significantly over the same period. In situ hybridization was used to examine receptor expression in subpopulations of SCG neurons identified using retrograde tracing. Eighteen to 20 h following local treatment of iris and CV with NGF, NT3 or vehicle, expression of NT receptor protein and mRNA was higher in iris‐ compared with CV‐projecting neurons from both young and old rats. NGF and NT3 treatment had no effect on NT receptor expression in CV‐projecting neurons at either age. However, similar treatment up‐regulated p75 and trkA expression in iris‐projecting neurons from 3‐month‐old, but not 24‐month‐old, rats. We conclude that lifelong exposure to low levels of NTs combined with impaired plasticity of NT receptor expression are predictors of neuronal vulnerability to age‐related atrophy.