Journal of the autonomic nervous system最新文献

{"title":"Index","authors":"","doi":"10.1016/S0165-1838(00)00161-2","DOIUrl":"https://doi.org/10.1016/S0165-1838(00)00161-2","url":null,"abstract":"","PeriodicalId":17228,"journal":{"name":"Journal of the autonomic nervous system","volume":"81 1","pages":"Pages 297-298"},"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)00161-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91658410","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":"Role of gap junctions in acetylcholine-induced vasodilation of proximal and distal arteries of the rat mesentery","authors":"Caryl E Hill,&nbsp;Haruyo Hickey,&nbsp;Shaun L Sandow","doi":"10.1016/S0165-1838(00)00113-2","DOIUrl":"10.1016/S0165-1838(00)00113-2","url":null,"abstract":"<div><p>We have previously shown that myoendothelial gap junctions are more prevalent in distal than in proximal arteries of the rat mesentery. In the present study we have investigated the role of gap junctions in the mechanism of action of endothelium-derived hyperpolarizing factor (EDHF) in these same vessels following relaxation with acetylcholine. Arteries were pre-constricted with phenylephrine and concentration response curves to acetylcholine were constructed in the presence of <em>N</em>^G-nitro-<span>l</span>-arginine methyl ester (<span>l</span>-NAME; 10⁻⁵ M) and indomethacin (10⁻⁵ M) to prevent effects due to the release of nitric oxide and prostacyclins. Nitric oxide was found to have only a small role in the relaxation of the proximal vessels and was not involved in the relaxations of the distal vessels. 18α-Glycyrrhetinic acid (10⁻⁵ M), a putative gap junction uncoupler, significantly reduced acetylcholine-induced relaxations by 50% in both proximal and distal vessels. Potassium channel antagonists, tetraethylammonium chloride (TEA; 10⁻³ M) and barium chloride (10⁻⁴ M), together abolished the dilatory response in the proximal mesenteric arteries, but did not completely block responses in the distal arteries. The data suggest that gap junctions contribute significantly to the acetylcholine-induced relaxation in both proximal and distal arteries of the rat mesentery. We hypothesize that the absence of a correlation between the role of gap junctions and the incidence of myoendothelial gap junctions in these same vessels is due to significant effects of the inhibitors on gap junctions located in the smooth muscle layers of the larger vessels.</p></div>","PeriodicalId":17228,"journal":{"name":"Journal of the autonomic nervous system","volume":"81 1","pages":"Pages 122-127"},"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)00113-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21712041","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":"In search of selective P2 receptor ligands: interaction of dihydropyridine derivatives at recombinant rat P2X2 receptors","authors":"Kenneth A Jacobson ,&nbsp;Yong-Chul Kim ,&nbsp;Brian F King","doi":"10.1016/S0165-1838(00)00128-4","DOIUrl":"10.1016/S0165-1838(00)00128-4","url":null,"abstract":"<div><p>1,4-Dihydropyridines are regarded as privileged structures for drug design, i.e. they tend to bind to a wide variety of receptor sites. We have shown that upon appropriate manipulation of the substituent groups on a 1,4-dihydropyridine template, high affinity and selectivity for the A₃ subtype of adenosine receptors (‘P1 receptors’) may be attained. In the present study we have begun to extend this approach to P2 receptors which are activated by ATP and other nucleotides. Nicardipine, a representative dihydropyridine, used otherwise as an L-type calcium channel blocker, was shown to be an antagonist at recombinant rat P2X₂ (IC₅₀=25 μM) and P2X₄ (IC₅₀ ∼220 μM) receptors expressed in <em>Xenopus</em> oocytes. Thus, this class of compounds represents a suitable lead for enhancement of affinity through chemical synthesis. In an attempt to modify the 1,4-dihydropyridine structure with a predicted P2 receptor recognition moiety, we have replaced one of the ester groups with a negatively charged phosphonate group. Several 4-phenyl-5-phosphonato-1,4-dihydropyridine derivatives, MRS 2154 (2,6-dimethyl), MRS 2155 (6-methyl-2-phenyl), and MRS 2156 (2-methyl-6-phenyl), were synthesized through three component condensation reactions. These derivatives were not pure antagonists of the effects of ATP at P2X₂ receptors, rather were either inactive (MRS 2156) or potentiated the effects of ATP in a concentration-dependent manner (MRS 2154 in the 0.3–10 μM range and MRS 2155 at &gt;1 μM). Antagonism of the effects of ATP at P2X₂ receptor superimposed on the potentiation was also observed at &gt;10 μM (MRS 2154) or 0.3–1 μM (MRS 2155). Thus, while a conventional dihydropyridine, nicardipine, was found to antagonize rat P2X₂ receptors ninefold more potently than P2X₄ receptors, the effects of novel, anionic 5-phosphonate analogues at the receptor were more complex.</p></div>","PeriodicalId":17228,"journal":{"name":"Journal of the autonomic nervous system","volume":"81 1","pages":"Pages 152-157"},"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)00128-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21712045","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 discovery and development of P2 receptor subtypes","authors":"Charles Kennedy","doi":"10.1016/S0165-1838(00)00133-8","DOIUrl":"10.1016/S0165-1838(00)00133-8","url":null,"abstract":"<div><p>Extracellular purine and pyrimidine nucleotides modulate cellular activity by acting at P2 receptors. The first receptor to be identified was the P₂-purinoceptor, which was characterised and named in 1978. In the 1980s this site was subdivided into P_2X and P_2Y purinoceptors on the basis of pharmacological criteria in functional studies on native receptors. Subsequently, a similar approach led to the characterisation of the P_2T, P_2Z, P_2U and P_2D purinoceptors. In the 1990s a molecular biological approach has led to the cloning and functional expression of at least 12 mammalian P2 receptor subtypes. The challenge now is to relate these recombinant receptors to native receptors present within a wide range of tissues.</p></div>","PeriodicalId":17228,"journal":{"name":"Journal of the autonomic nervous system","volume":"81 1","pages":"Pages 158-163"},"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)00133-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21712046","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":"P2X receptors mediate ATP-induced primary nociceptive neurone activation","authors":"Philip A Bland-Ward ,&nbsp;Patrick P.A Humphrey","doi":"10.1016/S0165-1838(00)00122-3","DOIUrl":"10.1016/S0165-1838(00)00122-3","url":null,"abstract":"<div><p>ATP-gated P2X ion-channel receptors are localised throughout the mammalian nervous system and have been identified on neurones which participate in conduction of nociceptive information from the periphery to, and within, the CNS. This article briefly reviews recently published research describing the role that ATP and P2X receptors may play in pain perception, highlighting the importance of the P2X₃ receptor in this process. The P2X₃ receptor subunit is almost exclusively expressed on a subset of small and medium diameter sensory neurones innervating cutaneous and visceral tissue. Activation of P2X receptors present on the peripheral terminals of primary afferents results in neuronal depolarisation and, in conscious animals, leads to the manifestation of acute nociceptive behaviour. Recent animal studies have also shown that P2X₃ receptor expression is increased in sensory ganglia following acute neuronal injury, hinting that similar plasticity in the expression of this receptor subtype could underlie the mechanisms involved in a range of conditions characterised by sensory hypersensitivity in man. It is apparent from the evidence available that functional antagonists at specific P2X receptor subtypes could represent an important class of novel analgesic agents.</p></div>","PeriodicalId":17228,"journal":{"name":"Journal of the autonomic nervous system","volume":"81 1","pages":"Pages 146-151"},"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)00122-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21712044","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":"Electrophysiology of autonomic neuromuscular transmission involving ATP","authors":"Peter Sneddon","doi":"10.1016/S0165-1838(00)00141-7","DOIUrl":"10.1016/S0165-1838(00)00141-7","url":null,"abstract":"<div><p>Electrophysiological investigations of autonomic neuromuscular transmission have provided great insights into the role of ATP as a neurotransmitter. Burnstock and Holman made the first recordings of excitatory junction potentials (e.j.p.s) produced by sympathetic nerves innervating the smooth muscle of the guinea-pig vas deferens. This led to the identification of ATP as the mediator of e.j.p.s in this tissue, where ATP acts as a cotransmitter with noradrenaline. The e.j.p.s are mediated solely by ATP acting on P2X₁ receptors leading to action potentials and a rapid phasic contraction, whilst noradrenaline mediates a slower, tonic contraction which is not dependent on membrane depolarisation. Subsequent electrophysiological studies of the autonomic innervation of smooth muscles of the urogenital, gastrointestinal and cardiovascular systems have revealed a similar pattern of response, where ATP mediates a fast electrical and mechanical response, whilst another transmitter such as noradrenaline, acetylcholine, nitric oxide or a peptide mediates a slower response. The modulation of junction potentials by a variety of pre-junctional receptors and the mechanism of inactivation of ATP as a neurotransmitter will also be described.</p></div>","PeriodicalId":17228,"journal":{"name":"Journal of the autonomic nervous system","volume":"81 1","pages":"Pages 218-224"},"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)00141-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21713038","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":"ATP, P2X receptors and pain pathways","authors":"Yanning Ding,&nbsp;Paolo Cesare,&nbsp;Liam Drew,&nbsp;Dimitra Nikitaki,&nbsp;John N Wood","doi":"10.1016/S0165-1838(00)00131-4","DOIUrl":"10.1016/S0165-1838(00)00131-4","url":null,"abstract":"<div><p>A role for ATP in nociception and pain induction was proposed on the basis of human psychophysical experiments shortly after the formulation of the purinergic hypothesis. Following the pharmacological definition of distinct P2X and P2Y purinergic receptor subtypes by Burnstock and his collaborators, molecular cloning studies have identified the gene products that underlie the effects of ATP on peripheral sensory neurons. One particular receptor, P2X₃, is of particular interest in the context of pain pathways, because it is relatively selectively expressed at high levels by nociceptive sensory neurons. Evidence that this receptor may play a role in the excitation of sensory neurons has recently been complemented by studies that suggest an additional presynaptic role in the regulation of glutamate release from primary afferent neurons in the dorsal horn of the spinal cord. In this brief review, we discuss the present state of knowledge of the role of ATP in pain induction through its action on peripheral P2X receptors.</p></div>","PeriodicalId":17228,"journal":{"name":"Journal of the autonomic nervous system","volume":"81 1","pages":"Pages 289-294"},"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)00131-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21712353","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":"A novel gliotic P2 receptor mediating cyclooxygenase-2 induction in rat and human astrocytes","authors":"Roberta Brambilla ,&nbsp;Stefania Ceruti ,&nbsp;Walter Malorni ,&nbsp;Flaminio Cattabeni ,&nbsp;Maria P Abbracchio","doi":"10.1016/S0165-1838(00)00152-1","DOIUrl":"10.1016/S0165-1838(00)00152-1","url":null,"abstract":"<div><p>In astrocytic cultures maintained <em>in vitro,</em> a brief challenge with the ATP analog α,βmethyleneATP (α,βmeATP) results, 3 days later, in marked elongation of astrocytic processes, an event that resembles the astrocytic hypertrophy known to occur in vivo during reactive astrogliosis. α,βmeATP-induced effects were observed in primary astrocytes obtained from both rat striatum and cortex (a brain area highly involved in chronic neurodegenerative pathologies), as well as in human astrocytoma cells (ADF cells). Purine-induced gliosis could be reversed by the non-selective P2X/P2Y receptor antagonist pyridoxalphosphate-6-azophenyl-2′,4′-disulphonic acid (PPADS), but not by oxidized ATP (an antagonist of the P2X₇ receptor), in line with previous studies of our laboratory suggesting the involvement of a P2Y receptor subtype. Induction of reactive gliosis was preceded by increased expression of cyclooxygenase-2 (COX-2), an enzyme whose excessive activation has been implicated in both acute and chronic neurodegenerative diseases. The selective COX-2 inhibitor NS-398 prevented both purine-induced astrogliosis and the associated COX-2 induction, suggesting that inhibition of the transcription of the COX-2 gene may also contribute to the anti-inflammatory properties of this agent. Significant blockade of both α,βmeATP-mediated reactive gliosis and COX-2 induction was also observed with PPADS. These data suggest that COX-2 mediates P2Y receptor-induced reactive astrogliosis, and that antagonists selective for this receptor subtype may represent a novel class of anti-inflammatory agents of potential interest in acute and chronic neurological disorders characterized by an inflammatory component and reactive gliosis.</p></div>","PeriodicalId":17228,"journal":{"name":"Journal of the autonomic nervous system","volume":"81 1","pages":"Pages 3-9"},"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)00152-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21712770","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":"Sensing arterial CO2 levels: a role for medullary P2X receptors","authors":"K.M Spyer,&nbsp;T Thomas","doi":"10.1016/S0165-1838(00)00118-1","DOIUrl":"10.1016/S0165-1838(00)00118-1","url":null,"abstract":"<div><p>ATP has been shown to act as an excitatory neurotransmitter in the central nervous system. In this review, evidence is presented to indicate that when ATP is micro-injected into the ventrolateral medulla (VLM) of the rat, changes in respiratory activity are elicited. These effects, and accompanying changes in heart rate and blood pressure are mediated by P2X purinoreceptors. Immunocytochemistry indicates a prevalence of P2X₂ and P2X₆ purinoreceptors in this region of the medulla. The P2 purinoceptor antagonists, suramin and PPADS blunt the respiratory responses to changes in arterial CO₂ levels when micro-injected into the VLM. This effect is shown electrophysiologically to be mediated by purinoreceptors located primarily on respiratory neurones of the VLM including the Bötzinger complex. As the effects of agonist activation of P2X₂ purinoceptors expressed in HEK293 cells and <em>Xenopus</em> oocytes are potentiated by lowering pH, these data imply that the central respiratory response to CO₂ depends in part on the pH sensitivity of purinoreceptors located on inspiratory neurones. The implications for respiratory activity and control are discussed.</p></div>","PeriodicalId":17228,"journal":{"name":"Journal of the autonomic nervous system","volume":"81 1","pages":"Pages 228-235"},"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)00118-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21713040","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":"Presynaptic P2 receptors?","authors":"T.W Stone,&nbsp;E.M O’Kane,&nbsp;M.-R Nikbakht,&nbsp;F.M Ross","doi":"10.1016/S0165-1838(00)00121-1","DOIUrl":"10.1016/S0165-1838(00)00121-1","url":null,"abstract":"<div><p>Although the emphasis in ATP research has been on postjunctional receptors, there is also evidence for presynaptic receptors regulating transmitter release in the autonomic nervous system. Recent work has attempted to identify similar mechanisms in the central nervous system. Some of the existing results can be explained by the metabolism of nucleotides to adenosine or adenosine 5′-monophosphate (AMP). However, studies of presynaptic effects using sensitive electrophysiological tests such as paired-pulse interactions indicate that nucleotides can act at presynaptic sites, but that their effects may be mediated by a release of adenosine. Results are also described which indicate that, under some conditions, nucleotides can mediate phenomena such as long-term potentiation, which probably involves a significant presynaptic element. In part these effects may involve a nucleotide-induced release of adenosine and the simultaneous activation of P1 and P2 receptors.</p></div>","PeriodicalId":17228,"journal":{"name":"Journal of the autonomic nervous system","volume":"81 1","pages":"Pages 244-248"},"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)00121-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21713042","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}