Archives internationales de pharmacodynamie et de therapie最新文献_第9页

Nitric oxide as a neurotransmitter in human airways. 一氧化氮是人体呼吸道中的一种神经递质。

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

M G Belvisi, J K Ward, J A Mitchell, P J Barnes

{"title":"Nitric oxide as a neurotransmitter in human airways.","authors":"M G Belvisi, J K Ward, J A Mitchell, P J Barnes","doi":"","DOIUrl":"","url":null,"abstract":"Human airway smooth muscle possesses a prominent nonadrenergic noncholinergic (i-NANC) bronchodilator response. Nitric oxide (NO) appears to account for all the i-NANC response in human central and peripheral airways in vitro. Furthermore, it appears that i-NANC relaxations in human trachea are associated with a concomitant selective elevation of cGMP, but not cAMP levels, which are inhibited by an NO synthase (NOS) inhibitor. This confirms the hypothesis that the L-arginine/NO/cGMP pathway is responsible for mediating the i-NANC response in this tissue. It is not certain from where the NO is formed or the location of the NOS enzyme. However, in human trachea, NOS immunoreactivity (NOS-IR) has been described in nerve fibres originating from intrinsic neurons. In addition, the density of NOS-IR is reduced from proximal to distal airways and this correlates with functional data describing a reduced i-NANC relaxation response from central to peripheral airways. The i-NANC bronchodilator nerves are the only neural relaxant pathway in human airways and, therefore, it is important to determine whether there is any defect in the ability of these nerves to function in diseased airways. In fact, functional and immunohistochemical data suggest that there may be a deficiency in NOS-IR nerves leading to a decreased i-NANC response in tissue from patients with cystic fibrosis. NOS inhibitors appear to enhance the cholinergic bronchoconstriction in human airways in vitro. Therefore, if the nitrergic innervation is dysfunctional in inflammatory conditions, its absence may lead to exaggerated bronchoconstriction.","PeriodicalId":8166,"journal":{"name":"Archives internationales de pharmacodynamie et de therapie","volume":"329 1","pages":"97-110"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18643382","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

Proceedings of the 3rd Workshop on Nonadrenergic Noncholinergic Mechanisms. Ghent, September 22-23, 1994. 第三届非肾上腺素能非胆碱能机制研讨会论文集。1994年9月22日至23日，根特。

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

引用次数: 0

Tachykinin receptors and receptor subtypes. 速激素受体和受体亚型。

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

R Patacchini, C A Maggi

{"title":"Tachykinin receptors and receptor subtypes.","authors":"R Patacchini, C A Maggi","doi":"","DOIUrl":"","url":null,"abstract":"The tachykinins, substance P, neurokinin A and neurokinin B, are a family of neuropeptides widely distributed in the mammalian central and peripheral nervous system. In the peripheral nervous system, tachykinins released from peripheral endings of sensory nerves are responsible for the neurogenic inflammation phenomenon. In the spinal cord/central nervous system, tachykinins play a role in pain transmission/perception and in some autonomic reflexes and behaviors. Their actions are mediated by three distinct receptors, termed NK1, NK2 and NK3. All tachykinin receptors belong to the superfamily of G protein-coupled receptors, with seven putative transmembrane spanning segments. In the past few years, a number of potent and selective antagonists, of both peptide and nonpeptide nature, has been developed for the NK1, NK2 and NK3 receptors. The contemporary isolation and cloning of the three tachykinin receptors enable now to study the molecular determinants for the interaction of natural tachykinins with their receptors, and the mechanism by which the antagonists interfere in this process. Furthermore, the introduction of tachykinin antagonists has revealed a striking species-related heterogeneity among the tachykinin receptors, and has also suggested a possible intra-species heterogeneity for both NK1 and NK2 receptors. However, molecular biology studies are needed to prove the existence of true tachykinin receptor subtypes.","PeriodicalId":8166,"journal":{"name":"Archives internationales de pharmacodynamie et de therapie","volume":"329 1","pages":"161-84"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18645521","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 nitrergic transmitter of the anococcygeus--NO or not? 无尾肌的氮递质——NO还是NO ?

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

A Gibson, S R Brave, I McFadzean, J F Tucker, C Wayman

{"title":"The nitrergic transmitter of the anococcygeus--NO or not?","authors":"A Gibson, S R Brave, I McFadzean, J F Tucker, C Wayman","doi":"","DOIUrl":"","url":null,"abstract":"Nonadrenergic noncholinergic (NANC) relaxations of the anococcygeus muscle are reduced by inhibitors of nitric oxide synthase (NOS). Since NOS can be detected within 6-hydroxydodpamine-resistant nerve tracts running through the muscle, it seems clear that these NANC relaxations result from activation of the L-arginine/NO pathway within the prejunctional nerve terminal, an example of so-called \"nitrergic\" transmission. However, a number of substances (hydroquinone, superoxide anions, hydroxocobalamin) profoundly reduce relaxations to exogenous NO but do not affect those to nitrergic field stimulation; such observations have raised questions over the nature of the substance actually released from the nitrergic nerves. Several possible explanations are discussed: (1) NO is released attached to a carrier molecule, perhaps in the form of a nitrosothiol; (2) NO is released in a modified redox form; (3) NO is released as a free radical, but is protected within the neuroeffector junction by other substances which preferentially interact with scavenger molecules; and (4) NO is released as a free radical and, because of a rapid and unhindered rate of diffusion over short distances (100-200 microM), it is less susceptible than exogenous NO to scavenger molecules. As yet, there is insufficient experimental evidence to decide which, if any, of these explanations is correct.","PeriodicalId":8166,"journal":{"name":"Archives internationales de pharmacodynamie et de therapie","volume":"329 1","pages":"39-51"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18551253","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

Adenosine receptors: protein and gene structure. 腺苷受体:蛋白质和基因结构。

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

M E Olah, H Ren, G L Stiles

{"title":"Adenosine receptors: protein and gene structure.","authors":"M E Olah, H Ren, G L Stiles","doi":"","DOIUrl":"","url":null,"abstract":"Adenosine produces a wide variety of effects throughout the body via activation of cell surface adenosine receptors. Adenosine receptors belong to the family of seven transmembrane domain G protein-coupled receptors and four subtypes have been cloned from a variety of species: the A1AR, A2aAR, A2bAR and A3AR. With a knowledge of both the protein sequence of adenosine receptors and the structure of the A1AR gene, the function and regulation of these receptors can be further explored. Site-directed mutagenesis of the A1AR has resulted in the identification of amino acid residues in transmembrane domains 6 and 7 that are critical in both agonist and antagonist binding. The construction and analysis of A1/A3 chimeric receptors has also revealed regions of adenosine receptors important in ligand binding. These include the distal region of the second extracellular loop of adenosine receptors, which has a role in the binding of both agonist and antagonist ligands. A segment of the exofacial portion of the transmembrane domain 5 of adenosine receptors appears to be involved in the selective recognition of agonist ligands containing a substitution at the 5'-position of the ribose moiety. Isolation of the genomic sequence of the human A1AR, in combination with analysis of the transcript distribution in several tissues, indicates that alternative splicing of the human A1AR occurs in the 5'-untranslated region of the gene. Two distinct transcripts, containing either exons 3, 5 and 6 or exons 4, 5 and 6, exist with exons 3 and 4 apparently mutually exclusive. The exon 4, 5 and 6 transcript has been detected in all tissues that express the A1AR, while the exon 3, 5 and 6 mRNA is found in tissues that display a relatively high A1AR expression. Findings suggest that the presence of two ATG codons in exon 4, upstream of the translation start site, is involved in the repression of the A1AR expression in those tissues containing the exon 4, 5 and 6 transcript.","PeriodicalId":8166,"journal":{"name":"Archives internationales de pharmacodynamie et de therapie","volume":"329 1","pages":"135-50"},"PeriodicalIF":0.0,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18645518","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

Analysis of 16,16-dimethylprostaglandin E2-induced diarrhea in cecectomized rats. 16,16-二甲基前列腺素e2致盲肠切除大鼠腹泻分析。

Archives internationales de pharmacodynamie et de therapie Pub Date : 1994-11-01

I Shimizu, K Kawashima, N Yoshida, T Ito

{"title":"Analysis of 16,16-dimethylprostaglandin E2-induced diarrhea in cecectomized rats.","authors":"I Shimizu, K Kawashima, N Yoshida, T Ito","doi":"","DOIUrl":"","url":null,"abstract":"The 16,16-dimethylprostaglandin E2 (dmPGE2)-induced diarrhea was analyzed in cecectomized rats prepared by resecting the cecum and its vasculature without disturbing the ileocecal junction. dmPGE2 (0.1-1.0 mg/kg, p.o.) dose-dependently increased the number of defecation episodes and induced a soft and watery stool in cecectomized rats. At 0.3 mg/kg, the diarrhea-inducing effects of dmPGE2 were more pronounced in cecectomized than in control rats. When given i.p., dmPGE2 (0.3 mg/kg) induced a watery stool in cecectomized and control rats with the same efficacy, although these effects were short-lasting as compared to oral administration. Castor oil (4 ml/kg, p.o.) also induced diarrhea, but did not produce a watery stool in cecectomized rats. There were no differences between cecectomized and control rats in basal small intestinal transits or in dmPGE2 (0.3 mg/kg, p.o.)-induced enhancements. Moreover, the basal and dmPGE2-induced jejunal net fluid transfers were the same in cecectomized and in control rats. On the other hand, the enhanced secretion of colonic fluid by dmPGE2, given intraluminally, was only half of that in control rats, whereas the colonic transit-enhancing effect of dmPGE2 in cecectomized rats was more pronounced than in control rats at 15 but not at 30 min after its administration. The basal colonic fluid contents and transits were the same in cecectomized and in control rats. Loperamide and morphine (0.1 and 1.0 mg/kg, s.c.) inhibited the dmPGE2 (0.3 mg/kg, p.o.)-induced diarrhea in cecectomized rats. N-methyllevallorphan (5 mg/kg, s.c.) completely antagonized the inhibitory effect of loperamide and partly antagonized the effect of morphine. These results suggest that oral administration of dmPGE2 induces a more pronounced secretory diarrhea in cecectomized than in control rats, probably due to the lack of the reservoir function of the cecum in the operated animals. This secretory diarrhea model is suitable for evaluating the antidiarrheal activity of drugs.","PeriodicalId":8166,"journal":{"name":"Archives internationales de pharmacodynamie et de therapie","volume":"328 3","pages":"326-43"},"PeriodicalIF":0.0,"publicationDate":"1994-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18630667","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

Effect of Y-25130, a selective 5-hydroxytryptamine3 receptor antagonist, on gastric emptying in mice. 5-羟色胺3受体拮抗剂Y-25130对小鼠胃排空的影响。

Archives internationales de pharmacodynamie et de therapie Pub Date : 1994-11-01

K Haga, K Asano, K Inaba, Y Morimoto, M Setoguchi

{"title":"Effect of Y-25130, a selective 5-hydroxytryptamine3 receptor antagonist, on gastric emptying in mice.","authors":"K Haga, K Asano, K Inaba, Y Morimoto, M Setoguchi","doi":"","DOIUrl":"","url":null,"abstract":"The effect of Y-25130 on gastric emptying of nutrient test meals (solid chow) was examined in mice. In a dose range of 0.01-1 mg/kg, p.o., Y-25130 significantly accelerated gastric emptying of solid meals in a dose-dependent manner, at an ED30 of 0.021 mg/kg. Other 5-hydroxytryptamine3 receptor antagonists and prokinetic agents having 5-hydroxytryptamine3 receptor antagonistic properties accelerated the emptying of solid meals in the following rank order of potency: Y-25130 = granisetron > or = tropisetron > ondansetron > cisapride > metoclopramide. The acceleration of the gastric emptying showed a good correlation with the antagonistic potencies of these compounds on 5-hydroxytryptamine3 receptors, determined by the inhibition test of the von Bezold-Jarisch reflex in anesthetized rats (r2 = 0.99). Domperidone (1 and 10 mg/kg, p.o.) and trimebutine (10 and 100 mg/kg, p.o.) failed to increase the rate of emptying from the stomach. Cisplatin (30 mg/kg, i.p.), a chemotherapeutic agent, significantly delayed the gastric emptying of solid meals, and Y-25130 (0.1-1 mg/kg, p.o.) prevented such a delay in emptying in a dose-dependent manner. These results suggest that Y-25130 accelerates the gastric emptying in mice by antagonism of the 5-hydroxytryptamine3 receptor.","PeriodicalId":8166,"journal":{"name":"Archives internationales de pharmacodynamie et de therapie","volume":"328 3","pages":"344-55"},"PeriodicalIF":0.0,"publicationDate":"1994-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18632611","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

Effects of chronic caffeine on adenosine, dopamine and acetylcholine systems in mice. 慢性咖啡因对小鼠腺苷、多巴胺和乙酰胆碱系统的影响

Archives internationales de pharmacodynamie et de therapie Pub Date : 1994-11-01

D Shi, O Nikodijević, K A Jacobson, J W Daly

{"title":"Effects of chronic caffeine on adenosine, dopamine and acetylcholine systems in mice.","authors":"D Shi, O Nikodijević, K A Jacobson, J W Daly","doi":"","DOIUrl":"","url":null,"abstract":"Chronic ingestion of caffeine by male NIH Swiss strain mice leads in about 3 days to a significant increase in A1-adenosine, nicotinic and muscarinic receptors, and a significant decrease of beta 1-adrenoceptors in cerebral cortical membranes. Plasma levels of caffeine in the chronically treated mice range from 0.70 to 5.7 micrograms/ml. The changes in receptors reverse after withdrawal of caffeine within 7 days. An increase in nitrendipine binding sites, associated with L-type calcium channels, also occurs within 4 days and has reversed in 7 days after withdrawal. There is no change in the levels of striatal nicotinic receptors of D2-dopamine receptors, nor of [3H]cocaine binding to dopamine uptake sites. Levels of opioid receptors are either increased (delta) or unaltered (mu, kappa). sigma-Receptors are unaltered. Stimulations of striatal adenylate cyclase by forskolin, dopamine and NECA are not significantly affected after chronic caffeine ingestion. The adenosine agonist, NECA, reverses the amphetamine-elicited increases in locomotor activity and partly reverses the cocaine-elicited increases. The NECA dose-response curve is multiphasic (depression, stimulation and then depression) versus amphetamine in control mice, but only depressant versus amphetamine in chronic caffeine mice, while being multiphasic versus cocaine in both control and chronic caffeine mice. NECA reverses the stimulation of locomotor activity elicited by the muscarinic antagonist, scopolamine, and is more effective in the chronic caffeine mice. The behavioral depressant effects of the muscarinic agonist, oxotremorine, are not markedly altered after chronic caffeine ingestion.","PeriodicalId":8166,"journal":{"name":"Archives internationales de pharmacodynamie et de therapie","volume":"328 3","pages":"261-87"},"PeriodicalIF":0.0,"publicationDate":"1994-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3432916/pdf/nihms400496.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18630661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Salivary secretion and histopathological effects after single administration of the muscarinic agonist SNI-2011 in MRL/lpr mice. 单次给药毒蕈碱激动剂SNI-2011对MRL/lpr小鼠唾液分泌及组织病理学的影响。

Archives internationales de pharmacodynamie et de therapie Pub Date : 1994-11-01

Y Iwabuchi, M Katagiri, T Masuhara

引用次数: 0

Comparative vasodepressor effects of 3-pyridine derivatives possessing the cyanoamidine or amide structure in pithed rats. 具有氰胺或酰胺结构的3-吡啶衍生物对大鼠血管抑制作用的比较。

Archives internationales de pharmacodynamie et de therapie Pub Date : 1994-11-01

T Kashiwabara, T Nakajima, S Hasegawa, Y Tanaka, Y Okada, T Izawa, N Ogawa

{"title":"Comparative vasodepressor effects of 3-pyridine derivatives possessing the cyanoamidine or amide structure in pithed rats.","authors":"T Kashiwabara, T Nakajima, S Hasegawa, Y Tanaka, Y Okada, T Izawa, N Ogawa","doi":"","DOIUrl":"","url":null,"abstract":"The potency and mechanism of the vasodepressor action of N-cyano-3-pyridinecarboximidamide and nicotinamide, which are 3-pyridine derivatives possessing cyanoamidine and amide structures, respectively, were studied in pithed rats infused with phenylephrine. The N-substituents of cyanoamidine and amide in the derivatives studied comprised 2-nitroxyethyl (KRN2391 and nicorandil), phenethyl (Ki769 and Ki765) and 2-(2-chlorophenyl)ethyl (Ki3005 and Ki4261) moieties. These derivatives produced vasodepressor actions in a dose-dependent manner, except for Ki4261 which did not show any action below the solubility limit. When the vasodepressor effects of compounds possessing the same N-substituents in cyanoamidine and amide derivatives were compared, the potency of cyanoamidine derivatives was greater than that of amide derivatives, Ki3005 being the most potent. The vasodepressor effects of cyanoamidine and amide derivatives were antagonized by glibenclamide, although the antagonism of the depressor effects of KRN2391 and nicorandil was less pronounced than that of the other derivatives. These results suggest that N-substituents, in addition to the cyanoamidine structure, play an important role in determining the vasodepressor potencies of 3-pyridine derivatives. Furthermore, the vasodepressor effects of these derivatives appear to be based on their K+ channel-opening actions, although those of KRN2391 and nicorandil seem to be partly mediated by a nitrate-like action in addition to their K+ channel-opening action.","PeriodicalId":8166,"journal":{"name":"Archives internationales de pharmacodynamie et de therapie","volume":"328 3","pages":"297-306"},"PeriodicalIF":0.0,"publicationDate":"1994-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18630664","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