Archives internationales de pharmacodynamie et de therapie最新文献_第8页

Interactions of serotonin with multiple receptors and neurotransmitters in the guinea-pig isolated colon. 豚鼠离体结肠中血清素与多种受体和神经递质的相互作用。

Archives internationales de pharmacodynamie et de therapie Pub Date : 1995-01-01

M R Briejer, L M Akkermans, J A Schuurkes

{"title":"Interactions of serotonin with multiple receptors and neurotransmitters in the guinea-pig isolated colon.","authors":"M R Briejer, L M Akkermans, J A Schuurkes","doi":"","DOIUrl":"","url":null,"abstract":"The motor effects of 5-hydroxytryptamine (5-HT; serotonin) on the guinea-pig isolated proximal colon were studied and analyzed. A classical organ bath setup was used to measure the longitudinal muscle responses isotonically. 5-Hydroxytryptamine induced concentration-dependent contractions which were preceded by relaxations at low concentrations. By means of the neurotoxin, tetrodotoxin, the muscarinic cholinoceptor antagonist, atropine, and selective 5-HT receptor antagonists, it was shown that the contractions to 5-HT are mediated by 5-HT2A receptors, localized on the smooth muscle, and by 5-HT3 and 5-HT4 receptors, localized on cholinergic nerves. The relaxation was abolished by tetrodotoxin and appeared to be mediated by two 5-HT receptor subtypes; the pharmacological profile of the high affinity 5-HT receptor resembled that of 5-HT2C receptors though it displayed also pronounced differences. Subsequently, it was shown that nitric oxide is the mediator released by lower concentrations of 5-HT, while, at higher concentrations, adenosine triphosphate could be involved as an end neurotransmitter as well. No evidence for a peptidergic neurotransmitter, such as vasoactive intestinal polypeptide, was obtained. Results with two 5-HT analogues confirmed the presence of a dual 5-HT receptor system (high and low affinity) regulating each the release of a different neurotransmitter (nitric oxide and adenosine triphosphate, respectively). The above described results stress the important role of 5-HT as a neurotransmitter involved in gastrointestinal motility.","PeriodicalId":8166,"journal":{"name":"Archives internationales de pharmacodynamie et de therapie","volume":"329 1","pages":"121-33"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18645517","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}

引用次数: 0

The 5-hydroxytryptamine-nitric oxide connection: the key link in the initiation of migraine? 5-羟色胺-一氧化氮:偏头痛发病的关键环节?

Archives internationales de pharmacodynamie et de therapie Pub Date : 1995-01-01

J R Fozard

引用次数: 0

Sensory nerves, nitric oxide and NANC vasodilatation. 感觉神经，一氧化氮和NANC血管舒张。

Archives internationales de pharmacodynamie et de therapie Pub Date : 1995-01-01

P Holzer, C Wachter, A Heinemann, M Jocic, I T Lippe, M K Herbert

{"title":"Sensory nerves, nitric oxide and NANC vasodilatation.","authors":"P Holzer, C Wachter, A Heinemann, M Jocic, I T Lippe, M K Herbert","doi":"","DOIUrl":"","url":null,"abstract":"Primary afferent neurons, originating from the dorsal root ganglia, provide a perivascular network of fibres around the arterial system throughout the body. When stimulated, these fibres cause a nonadrenergic noncholinergic (NANC) vasodilatation by release of calcitonin gene-related peptide (CGRP). This peptide is a potent vasodilator and, in this action, cooperates with nitric oxide (NO) in a tissue-specific manner. The hyperaemic effect of intravascularly injected rat CGRP-alpha in the rat gastric mucosa is reduced by blockade of the NO synthesis, which indicates that CGRP dilates the gastric microvascular bed via NO-dependent and -independent mechanisms. This is also true for endogenous CGRP, as the gastric mucosal hyperaemia, which is caused by gastric acid challenge and involves CGRP, is likewise blocked by inhibition of the NO synthesis. The CGRP/NO-mediated vasodilatation is an important element of a neural emergency system that strengthens the resistance of the gastric mucosa in the face of pending acid injury. In the rat skin, CGRP participates in neurogenic inflammatory processes but the cutaneous vasodilator action of exogenous CGRP and the CGRP-mediated vasodilatation, evoked by antidromic stimulation of afferent nerve fibres, do not depend on the formation of NO. This L-arginine-derived autacoid, however, plays a role in the release of CGRP from afferent nerve fibres in the skin since it contributes to the CGRP-mediated vasodilator responses to chemical irritation or immunological challenge via interleukin-1 beta. These data indicate that the type of interaction between CGRP and NO in causing a NANC vasodilatation varies with the vascular bed under study. Depending on the tissue, NO may facilitate the release of CGRP from afferent nerve fibres or be a secondary vasorelaxant messenger of the peptide.","PeriodicalId":8166,"journal":{"name":"Archives internationales de pharmacodynamie et de therapie","volume":"329 1","pages":"67-79"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18645525","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}

引用次数: 0

Nitric oxide and bronchial hyperresponsiveness. 一氧化氮和支气管高反应性。

Archives internationales de pharmacodynamie et de therapie Pub Date : 1995-01-01 DOI: 10.1007/978-3-0348-8474-7_6

F. Nijkamp, G. Folkerts

引用次数: 108

Bioassay and pharmacological characterization of the nitrergic neurotransmitter. 氮能神经递质的生物测定和药理学特性。

Archives internationales de pharmacodynamie et de therapie Pub Date : 1995-01-01

G E Boeckxstaens, J G De Man, B Y De Winter, T G Moreels, A G Herman, P A Pelckmans

{"title":"Bioassay and pharmacological characterization of the nitrergic neurotransmitter.","authors":"G E Boeckxstaens, J G De Man, B Y De Winter, T G Moreels, A G Herman, P A Pelckmans","doi":"","DOIUrl":"","url":null,"abstract":"Based on organ bath experiments illustrating nitric oxide (NO) or an NO-releasing substance as mediator of the nonadrenergic noncholinergic (NANC) nerve-induced relaxations in the canine ileocolonic junction and rat gastric fundus, a bioassay superfusion technique was developed to detect and characterize the inhibitory NANC neurotransmitter. Evidence is provided that NANC nerve stimulation results in the release of a vasorelaxant factor with pharmacological properties similar to NO: its release is blocked by inhibition of the NO biosynthesis and tetrodotoxin, but enhanced by L-arginine. Its half-life is comparable to that of NO, and its biological activity is enhanced by superoxide dismutase, but abolished by hemoglobin. In addition, the nitrergic transferable factor is similarly affected as authentic NO by pyrogallol, hydroquione, hydroxocobalamin and L-cysteine. Nitrosothiols, like S-nitroso-L-cysteine, S-nitrosoglutathione and S-nitroso-N-acetyl-D,L- penicillamine, on the other hand, have a different pharmacological profile compared to NO and the nitrergic factor, indicating that NO, and not a nitrosothiol, is released from inhibitory NANC nerves in the canine ileocolonic junction. This nerve-induced release is Ca(2+)-dependent and prejunctionally regulated by K+ channels and alpha 2-adrenoceptors: blockade of K+ channels enhances the release, whereas alpha 2-adrenoceptor activation reduces the release of the nitrergic factor, possibly by activating K+ channels.","PeriodicalId":8166,"journal":{"name":"Archives internationales de pharmacodynamie et de therapie","volume":"329 1","pages":"11-26"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18643530","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}

引用次数: 0

Interplay of VIP and nitric oxide in the regulation of neuromuscular activity in the gut. VIP和一氧化氮在肠道神经肌肉活动调节中的相互作用。

Archives internationales de pharmacodynamie et de therapie Pub Date : 1995-01-01

K S Murthy, J R Grider, J G Jin, G M Makhlouf

引用次数: 0

Tachykinin antagonists and the airways. 速激肽拮抗剂和气道。

Archives internationales de pharmacodynamie et de therapie Pub Date : 1995-01-01

G F Joos, J C Kips, R A Peleman, R A Pauwels

{"title":"Tachykinin antagonists and the airways.","authors":"G F Joos, J C Kips, R A Peleman, R A Pauwels","doi":"","DOIUrl":"","url":null,"abstract":"There is now convincing evidence for the presence of substance P (SP) and neurokinin A (NKA) in human airway nerves. Studies on autopsy tissue, on bronchoalveolar lavage fluid and on sputum suggest that SP may be present in increased amounts in the asthmatic airway. Substance P and NKA are potent bronchoconstrictors of human airways, asthmatics being more sensitive than normal persons. The major enzyme responsible for the degradation of the tachykinins, the neutral endopeptidase, is present in the airways and is involved in the breakdown of exogenously administered SP and NKA, both in normal and asthmatic persons. Other, less well documented airway effects of SP and NKA include mucus secretion, vasodilation and plasma extravasation, as well as the chemoattraction and stimulation of various cells presumed to be involved in asthmatic airway inflammation. NK2 receptors and, to a lesser extent, NK1 receptors have been shown to be involved in bronchoconstriction, whereas NK1 receptors were found to be involved in mucus secretion, microvascular leakage and vasodilatation, and in most of the effects on inflammatory cells. The first clinical trial with FK224, a peptide NK1 and NK2 receptor antagonist, and CP99994, a nonpeptide NK1 receptor antagonist, are negative. However, FK224 failed to block the bronchoconstrictor effect of NKA in asthmatics and the dose of CP99994, needed to antagonize tachykinin effects in man, remains to be determined.","PeriodicalId":8166,"journal":{"name":"Archives internationales de pharmacodynamie et de therapie","volume":"329 1","pages":"205-19"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18549710","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}

引用次数: 0

Nitric oxide-mediated contraction in enteric smooth muscle. 一氧化氮介导的肠平滑肌收缩。

Archives internationales de pharmacodynamie et de therapie Pub Date : 1995-01-01

L Barthó, R A Lefebvre

{"title":"Nitric oxide-mediated contraction in enteric smooth muscle.","authors":"L Barthó, R A Lefebvre","doi":"","DOIUrl":"","url":null,"abstract":"Nitric oxide (NO) seems to be involved as neurotransmitter in nonadrenergic noncholinergic (NANC) smooth muscle relaxation throughout the gastrointestinal tract. Contractile responses to NO in the gastrointestinal smooth muscle have also been reported. In the guinea-pig ileal longitudinal muscle-myenteric plexus preparation at basal tone, NO induces a moderate relaxation followed by an aftercontraction; the latter is blocked by tetrodotoxin. The aftercontraction is also reduced by atropine, the remaining part being inhibited by a substance P antagonist. This indicates the activation of cholinergic and, possibly, tachykininergic neurons; it is not clear whether this represents a rebound phenomenon to the relaxation or a direct action of NO, initially masked by the relaxation. Nitrergic \"off\"-contractions, in response to electrical stimulation of the inhibitory NANC nerves, were reported in the opossum esophageal body and in the cat distal colon. Primary contractions to NO have been reported in the rat ileum and in the longitudinal muscle of the opossum esophagus. In the rat preparation, the contraction to NO is observed at lower concentrations than the relaxant effect. While the contraction in the opossum seems to be related to guanylate cyclase activation, this is not the case in the rat ileum, as methylene blue did not influence the contractions and 8-bromo-cGMP only had a relaxant effect. No clear-cut rise in cGMP was observed during the NO-induced contraction. The NO-induced contraction was also not influenced by ryanodine but it was concentration-dependently reduced by nifedipine, suggesting that it is related to extracellular calcium influx through L-type calcium channels. Primary contractions due to NO were also observed in the rat whole ileum and in the rat caecal longitudinal muscle, while aftercontractions, due to NO, were also obtained in the rat descending, transverse and sigmoid colon, as well as in the cat ileal longitudinal muscle.","PeriodicalId":8166,"journal":{"name":"Archives internationales de pharmacodynamie et de therapie","volume":"329 1","pages":"53-66"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18643385","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}

引用次数: 0

Characterization of the adenosine receptors in the airways. 气道中腺苷受体的表征。

Archives internationales de pharmacodynamie et de therapie Pub Date : 1995-01-01

R A Pauwels, G F Joos

引用次数: 0

Nitric oxide and bronchial hyperresponsiveness. 一氧化氮和支气管高反应性。

Archives internationales de pharmacodynamie et de therapie Pub Date : 1995-01-01

F P Nijkamp, G Folkerts

{"title":"Nitric oxide and bronchial hyperresponsiveness.","authors":"F P Nijkamp, G Folkerts","doi":"","DOIUrl":"","url":null,"abstract":"Increasing evidence points to an important role for nitric oxide in the regulation of pulmonary functions and in pulmonary disease. In the respiratory tract, sensory nerves, endothelial cells, vascular and airway smooth muscle cells, inflammatory cells and the airway epithelium are sources of nitric oxide. Different nitric oxide synthases have been isolated, cloned and sequenced. Functionally, there are constitutive and inducible forms of nitric oxide synthase. A number of cytokines have been shown to inhibit or induce the expression of the inducible nitric oxide synthase. In human airways, endogenous nitric oxide appears to account for the bronchodilator nonadrenergic and noncholinergic response. Nitric oxide-containing vasodilators, such as glyceryl trinitrate and sodium nitroprusside, induce relaxation of the isolated airway smooth muscle, activate guanylate cyclase and raise c-GMP levels. Nitric oxide (constitutive), produced by the epithelial layer, appears to be important in blunting the histamine contractile response of the airway tissue. Furthermore, tracheal relaxation by, e.g., bradykinin or potassium chloride, is mediated by the release of nitric oxide. The virus (Parainfluenza type 3)-induced airway hyperreactivity in guinea-pigs is correlated with a deficiency in endogenous constitutive nitric oxide production by the airways and can be blocked by low doses of L-arginine. In inflamed tissue, nitric oxide quickly reacts with superoxide anion, resulting in the formation of the toxic peroxynitrite which promotes lipid and sulfhydryl oxidation. Asthmatic patients have higher amounts of nitric oxide in the expired air, possibly due to the inflammation. This increased nitric oxide production can be inhibited by inhaled corticosteroids. The effect of inhaled nitric oxide on the lung function of asthmatic patients is variable. In contrast, low doses of inhaled nitric oxide are effective in reversing the pulmonary vasoconstriction. These results point to an important role for nitric oxide in modulating airway reactivity.","PeriodicalId":8166,"journal":{"name":"Archives internationales de pharmacodynamie et de therapie","volume":"329 1","pages":"81-96"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18643380","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}

引用次数: 0