Journal of the autonomic nervous system最新文献

{"title":"The effects of exercise and training on human cardiovascular reflex control","authors":"Saoirse E O’Sullivan,&nbsp;Christopher Bell","doi":"10.1016/S0165-1838(00)00148-X","DOIUrl":"10.1016/S0165-1838(00)00148-X","url":null,"abstract":"<div><p>During physical activity, there is a graded withdrawal of vagal cardiac tone and a graded increase in sympathetic cardiac and vasomotor tone, initiated through both central command from the somatic motor cortex and muscle chemoreceptive and mechanoreceptive inputs. In parallel, there is an upward resetting of the operating point of the arterial baroreflex, with preserved reflex sensitivity. In contrast to the traditional interpretation that blood flow through exercising muscle is independent of vasomotor neural influences because of the dominance of local dilator metabolites, recent evidence suggests that both constrictor and dilator sympathetic neural influences may be involved in determining absolute levels of perfusion. Post-exercise, there is a period of relative hypotension that is associated with decreased peripheral resistance. Some, but not all, evidence indicates a causal role for reduced sympathetic drive. Chronic exercise training appears to reduce resting sympathetic activity, with parallel changes in the gain of a variety of cardiovascular autonomic reflexes initiated from cardiovascular sites. These changes may be attributable at least partly to masking of arterial baroreflexes by the impact of elevated blood volume on low-pressure baroreceptors. The reductions in sympathetic drive that follow training are more pronounced in patients with essential hypertension than in normotensive individuals and are likely to underlie the anti-hypertensive effect of exercise.</p></div>","PeriodicalId":17228,"journal":{"name":"Journal of the autonomic nervous system","volume":"81 1","pages":"Pages 16-24"},"PeriodicalIF":0.0,"publicationDate":"2000-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0165-1838(00)00148-X","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21712772","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":"Functional properties of heteromeric P2X1/5 receptors expressed in HEK cells and excitatory junction potentials in guinea-pig submucosal arterioles","authors":"Annmarie Surprenant ,&nbsp;David A Schneider ,&nbsp;Heather L Wilson ,&nbsp;James J Galligan ,&nbsp;R.Alan North","doi":"10.1016/S0165-1838(00)00123-5","DOIUrl":"10.1016/S0165-1838(00)00123-5","url":null,"abstract":"<div><p>P2X receptors are ATP-gated cation channels; they form as homomers or heteromers from a family of seven related subunits. In particular, heteromeric channels comprising P2X₂ and P2X₃ subunits, or P2X₁ and P2X₅ subunits, show distinctive physiological and pharmacological properties in heterologous expression systems. There is substantial evidence that one of the native P2X receptors in sensory neurones corresponds to the P2X_2/3 heteromer, but there is no evidence for P2X_1/5 heteromers in native tissue. We recorded currents in response to activation of heteromeric P2X_1/5 receptors expressed in HEK293 cells to characterize further their functional properties. The ATP concentration–response curve had a threshold concentration of 1 nM, and a Hill slope of one. TNP-ATP was a weak partial agonist, and a non-competitive antagonist which inhibited maximal ATP currents by 60%. Increasing or decreasing pH from 7.3 shifted the ATP concentration–response curves to the right by fivefold and decreased the maximum current by 40%. Calcium permeability was lower than that observed for other P2X receptors (<em>P</em>_Ca/<em>P</em>_Na ratio=1.1). The nanomolar sensitivity of this receptor revealed a steady release of ATP from HEK293 cells, providing an extracellular concentration which ranged from 3 to 300 nM. Noradrenaline (0.3–30 μM) increased ATP-evoked currents by 35%; this facilitation occurred within 20 ms. We also recorded excitatory junction potentials (EJPs) from guinea-pig submucosal arterioles. EJPs were inhibited by suramin and PPADS (IC₅₀s of 0.2 μM and 20 μM) but TNP-ATP (0.1–10 μM) inhibited EJPs by &lt;30%. Noradrenaline (0.3–30 μM in the presence of phentolamine and propranolol) decreased EJPs in control preparations but facilitated EJPs by 5–20% in submucosal arterioles from reserpinized guinea-pigs. These properties are discussed in relation to P2X receptors underlying EJPs at autonomic neuroeffector junctions.</p></div>","PeriodicalId":17228,"journal":{"name":"Journal of the autonomic nervous system","volume":"81 1","pages":"Pages 249-263"},"PeriodicalIF":0.0,"publicationDate":"2000-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0165-1838(00)00123-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21713043","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":"P2 receptors in the kidney","authors":"Matthew A Bailey,&nbsp;Kate A Hillman,&nbsp;Robert J Unwin","doi":"10.1016/S0165-1838(00)00125-9","DOIUrl":"10.1016/S0165-1838(00)00125-9","url":null,"abstract":"<div><p>Our understanding of the actions of extracellular ATP in controlling kidney function via stimulation of P2 receptors is still at an early stage. Recently, several groups, including our own, have begun to address this subject: in this brief review, we discuss some of these effects and speculate on likely function of extracellular nucleotides in the kidney.</p></div>","PeriodicalId":17228,"journal":{"name":"Journal of the autonomic nervous system","volume":"81 1","pages":"Pages 264-270"},"PeriodicalIF":0.0,"publicationDate":"2000-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0165-1838(00)00125-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21713044","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":"Say NO to ET","authors":"P.M Vanhoutte","doi":"10.1016/S0165-1838(00)00126-0","DOIUrl":"10.1016/S0165-1838(00)00126-0","url":null,"abstract":"<div><p>The endothelial cells relase both relaxing [nitric oxide (NO), endothelium-derived hyperpolarizing factor (EDHF), prostacyclin] and contracting factors [endoperoxides, thromboxane A₂, superoxide anions, endothelin-1 (ET)]. The production of ET is inhibited by NO. The latter also strongly opposes the direct effects of the former on vascular smooth muscle. With aging and vascular disease, the production of enothelial NO declines, and thus ET can be released, act and contribute to the symptoms.</p></div>","PeriodicalId":17228,"journal":{"name":"Journal of the autonomic nervous system","volume":"81 1","pages":"Pages 271-277"},"PeriodicalIF":0.0,"publicationDate":"2000-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0165-1838(00)00126-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21713045","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":"Purinergic nerves and purinoceptors: early perspectives","authors":"David Satchell","doi":"10.1016/S0165-1838(00)00140-5","DOIUrl":"10.1016/S0165-1838(00)00140-5","url":null,"abstract":"<div><p>I have had the pleasure and privilege of being involved in one facet of Geoffrey Burnstock’s early career. I have reviewed this work together with more recent developments in the area. In 1968, the presence of non-adrenergic, non-cholinergic inhibitory nerves had been established but the identity of their neurotransmitter was unknown. Stimulation of these nerves in recycled perfused toad and guinea-pig stomachs caused release of adenosine and inosine. When ATP was added to recycled perfusates, it was broken down to adenosine and inosine. These findings together with information that AMP was released from stimulated, isolated turkey Auerbach’s plexus which was known to contain the nerves, suggested that ATP could be the neurotransmitter. This was supported by observations that ATP elicited responses similar to that of nerve stimulation in a variety of tissues. Developments from the early purinergic nerve hypothesis are considered including independence of extracellular actions of ATP from its intracellular actions, identification and cloning of purinoceptors and cotransmission of ATP with other substances.</p></div>","PeriodicalId":17228,"journal":{"name":"Journal of the autonomic nervous system","volume":"81 1","pages":"Pages 212-217"},"PeriodicalIF":0.0,"publicationDate":"2000-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0165-1838(00)00140-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21712509","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":"Regulated expression of the rat recombinant P2X3 receptor in stably transfected CHO-K1 tTA cells","authors":"Wilhelm G Lachnit ,&nbsp;Ian B Oglesby ,&nbsp;Joel R Gever ,&nbsp;Marina Gever ,&nbsp;Chiao-Chain Huang ,&nbsp;Xing Cheng Li ,&nbsp;Hong Jin ,&nbsp;Joseph G McGivern ,&nbsp;Anthony P.D.W Ford","doi":"10.1016/S0165-1838(00)00120-X","DOIUrl":"10.1016/S0165-1838(00)00120-X","url":null,"abstract":"<div><p>In this report, the regulatible expression by tetracycline of the rat recombinant P2X₃ receptor in stably transfected Chinese hamster ovary (CHO-K1) expressing the tetracycline-controlled transactivator (tTA) is described. cDNA encoding the rat P2X₃-receptor was subcloned into pTRE (a tetracycline-repressible expression vector) which was used to transfect stably CHO-K1 tTA cells. Using whole cell patch clamp techniques, 100 μM ATP evoked inward currents of 2.9±1.6 nA in transfected cells grown in the absence of tetracycline (<em>tet−</em>). The P2X₃ receptor protein was detectable by immunoblot as early as 24 h and protein expression levels continued to increase as much as 192 h following activation of tTA by the removal of the antibiotic. Saturation binding isotherms using [³⁵S]ATPγS yielded a p<em>K</em>_d of 8.2±0.1 and a <em>B</em>_max of 31.9±3.5 pmol/mg protein in <em>tet−</em> cell membranes and a p<em>K</em>_d of 8.1±0.1 and a <em>B</em>_max of 5.8±0.8 pmol/mg protein in <em>tet+</em> cell membranes. The agonist ligands 2MeSATP and αβMeATP displaced the binding of [³⁵S]ATPγS in <em>tet−</em> cell membranes with very high affinity, yielding pIC₅₀ values of 9.4±0.2 and 7.5±0.2, respectively. In <em>tet+</em> cell membrane, displacement of [³⁵S]ATPγS by 2MeSATP and αβMeATP was of much lower affinity (pIC₅₀ values of 7.8 and 6.2, respectively). ATP, ADP and UTP showed similar displacement of [³⁵S]ATPγS binding in <em>tet−</em> and <em>tet+</em> cell membranes. In other experiments, cytosolic Ca²⁺ was monitored using the fluorescent indicator, fluo-3. Increases in cytosolic Ca²⁺ were elicited by 100 nM αβMeATP in <em>tet−</em> cells while no increases in cytosolic Ca²⁺ were detected below 100 μM αβMeATP in either <em>tet+</em> cells or untransfected cells. These calcium responses to αβMeATP had a pEC₅₀ of 6.7 and were transient, returning to baseline within 120 s. Suramin produced concentration-dependent, parallel, dextral shifts of <em>E</em>/[<em>A</em>] curves to αβMeATP yielding a p<em>K</em>_B of 5.6. PPADS produced non-parallel, dextral shifts of <em>E</em>/[<em>A</em>] curves to αβMeATP which were insurmountable. These results show for the first time, expression of a functional, homomeric recombinant rat P2X₃ receptor which is under regulated expression in a stably transfected mammalian cell line.</p></div>","PeriodicalId":17228,"journal":{"name":"Journal of the autonomic nervous system","volume":"81 1","pages":"Pages 75-81"},"PeriodicalIF":0.0,"publicationDate":"2000-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0165-1838(00)00120-X","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21712656","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":"Purines: from premise to promise","authors":"Michael Williams","doi":"10.1016/S0165-1838(00)00153-3","DOIUrl":"10.1016/S0165-1838(00)00153-3","url":null,"abstract":"<div><p>Geoff Burnstock’s remarkable insight and tenacity has established the area of purinergic research as a bona fide target for drug discovery. While efforts in P1 receptor-based medicinal chemistry and biology efforts over the past 25 years have not reached the level of success that the pharmaceutical industry investment may have anticipated, the P2 area, with knowledge of the selective localization of members of the P2X and P2Y family members and data from transgenic knockouts, has identified several potential therapeutic areas of major promise including cystic fibrosis, chronic bronchitis, male contraception and neurodegeneration. In addition, interest in the potential of purinergic therapeutics has extended outside the major pharmaceutical companies to the ‘biotech industry’ resulting in an environment where the inherent risks of ‘first in field’ in a therapeutic area may be more appropriately nurtured.</p></div>","PeriodicalId":17228,"journal":{"name":"Journal of the autonomic nervous system","volume":"81 1","pages":"Pages 285-288"},"PeriodicalIF":0.0,"publicationDate":"2000-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0165-1838(00)00153-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21712352","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":"Alkylxanthines as research tools","authors":"John W Daly","doi":"10.1016/S0165-1838(00)00110-7","DOIUrl":"10.1016/S0165-1838(00)00110-7","url":null,"abstract":"<div><p>(1) The methylxanthine<span><span><span> caffeine has many pharmacological effects, most of which can be linked to blockade of adenosine receptors, inhibition of phosphodiesterases, and augmentation of calcium-dependent release of calcium from intracellular stores. (2) A variety of xanthines have been developed as potent and/or selective antagonists for adenosine receptors. (3) Several xanthines have been developed that are more potent and more selective inhibitors of cyclic nucleotide phosphodiesterase than caffeine or </span>theophylline. (4) Caffeine remains the xanthine of choice for activation of intracellular calcium-sensitive calcium release channels although millimolar concentrations are required, which can have effects on other aspects of </span>calcium regulation.</span></p></div>","PeriodicalId":17228,"journal":{"name":"Journal of the autonomic nervous system","volume":"81 1","pages":"Pages 44-52"},"PeriodicalIF":0.0,"publicationDate":"2000-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0165-1838(00)00110-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21712651","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":"NANC transmission at a varicosity: the individuality of single synapses","authors":"M.R Bennett","doi":"10.1016/S0165-1838(00)00149-1","DOIUrl":"10.1016/S0165-1838(00)00149-1","url":null,"abstract":"<div><p>Nerve terminals consist of several hundred varicosities or synapses, each with a single active zone. The smooth muscle membrane apposing varicosities within about 50 nm is occupied by a 1-μm diameter cluster of P2X₁ receptors together with a mixture of other P2X subtypes; the rest of the membrane possesses small (0.4 μm diameter) clusters of P2X₁ to P2X₆ subunits. The small P2X clusters appear to form large clusters during development. This is supported by the observation that chimeras of P2X₁ subunits and green fluorescent protein (P2X₁-GFP), when packaged into adenoviruses used to infect excitable cells, initially form a diffuse distribution of small clusters of P2X₁-GFP in the membrane; these can be later observed in real time to form large clusters. Recording the electrical signs of ATP release from single adjacent varicosities, or using antibodies to label the extent of exocytosis from them, shows that they release with quite different probabilities. There are large quantitative differences in the extent of P2X autoreceptors on the membranes of individual varicosities. These will contribute to the differences in the probability of secretion from individual varicosities. The present analysis of NANC transmission at single varicosities indicates that individual synapses possess different probabilities for the secretion of transmitter as well as different complements of autoreceptors and mixtures of postjunctional receptor subunits.</p></div>","PeriodicalId":17228,"journal":{"name":"Journal of the autonomic nervous system","volume":"81 1","pages":"Pages 25-30"},"PeriodicalIF":0.0,"publicationDate":"2000-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0165-1838(00)00149-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21712773","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":"Platelet P2 receptors: from curiosity to clinical targets","authors":"Noel J Cusack ,&nbsp;Susanna M.O Hourani","doi":"10.1016/S0165-1838(00)00151-X","DOIUrl":"10.1016/S0165-1838(00)00151-X","url":null,"abstract":"<div><p>Adenosine 5′-diphosphate (ADP) is a paracrine mediator that activates human blood platelets, causing them to become adhesive and thereby contributing to their role in hemostasis. The actions of ADP were initially thought to be mediated by a unique ADP receptor termed P2_T found only on platelets and antagonized by ATP, but it appears that at least two P2Y receptor subtypes are involved, a P2Y₁ receptor linked in some way to control of intracellular-free calcium levels and another P2Y receptor linked via an inhibitory G protein to adenylate cyclase. In addition, the presence of excitatory P2X₁ receptors that mediate the influx of monovalent and divalent cations in response to both ADP and ATP has been demonstrated. The precise contribution that each of these P2 receptors make to the overall phenomena associated with platelet aggregation, adhesion and hemostasis is yet to be defined. Antithrombotic agents that interfere with the actions of ADP are marketed, and P2 receptor antagonists are entering clinical trials for acute treatments of thrombosis. This review seeks to summarize the present state of knowledge of platelet P2 receptor pharmacology and therapeutics.</p></div>","PeriodicalId":17228,"journal":{"name":"Journal of the autonomic nervous system","volume":"81 1","pages":"Pages 37-43"},"PeriodicalIF":0.0,"publicationDate":"2000-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0165-1838(00)00151-X","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21712775","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}