Abstract:
:1. In the presence of atropine, mepyramine and ranitidine, electric field stimulation of the guinea-pig isolated ileum longitudinal muscle-myenteric plexus preparation resulted in a two component non-adrenergic non-cholinergic contraction. The initial contraction had a duration of approximately 1 s whereas the second contraction lasted approximately 10 s. The second contraction was completely inhibited by tetrodotoxin (0.2 x 10(-6) M) with minimal effect on the initial contraction. Phentolamine (3 x 10(-6) M), propranolol (3 x 10(-6) M) and hexamethonium (10(-4) M), did not significantly reduce either component of the contractile response. 2. The neurokinin NK1 receptor antagonists, GR82334 and GR71251, produced concentration-related (EC50 = 564 and 173 nM respectively) inhibitions of the second contraction with no effect on the initial contraction. The neurokinin NK2 receptor antagonists MEN 10207 and Ac-Leu-Asp-Gln-Trp-Phe-Gly-NH2 (R 396), 1 x 10(-9)-10(-5) M, were without effect on either component of the contractile response. 3. Concentration-related inhibitions of the second contraction, with no effect on the initial contraction, were observed after inclusion of the histamine H3 receptor agonists (R)-alpha-methylhistamine (pD2 = 7.6), N alpha-methylhistamine (pD2 = 7.7) and N alpha,N alpha-dimethylhistamine (pD2 = 6.3). Histamine also inhibited the second contraction (pD2 = 6.2) in a concentration-related manner but produced a lower maximum inhibitory effect than the other agonists tested. 4. Inclusion of the H3 receptor antagonists, thioperamide, burimamide, impromidine and phenylbutanoylhistamine, caused parallel concentration-related rightward shifts in the concentration-response curve to (R)-alpha-methylhistamine. In each case, Schild analysis of these data gave slopes not significantly different from unity. Antagonist affinity values for thioperamide (pA2 = 8.2), burimamide (pA2 = 7.0) and impromidine (pA2 = 7.0) were consistent with values obtained in other assays of the H3 receptor. However, phenylbutanoylhistamine (pA2 = 5.8) and betahistine (pKB < 4) had affinities more than ten fold lower than values obtained in other assays of the H3 receptor.5. Exposure of the tissues to N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (10-6 M) for 7-30min followed by extensive washing, had no effect on basal contractions, but produced a rightward shift in the concentration-response curves to (R-alpha-methylhistamine, Nalpha"-methylhistamine, Nalpha",Nalpha-dimethylhistamine and histamine. This treatment also resulted in a decrease in the maximum inhibitory response obtainable. Apparent agonist affinity (pKD) values of 7.01, 7.06, 6.09 and 6.13 were estimated for (R)-alpha-methylhistamine, Nalpha-methylhistamine, Nalpha',Nalpha"-dimethylhistamine and histamine respectively.6. In conclusion, pharmacological analysis has revealed that histamine H3 receptors in the guinea-pig ileum modulate the release of non-adrenergic non-cholinergic neurotransmitters, one of which is probably substance P. In addition we have identified N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline as an irreversible antagonist at H3 receptors and have used this compound to estimate apparent affinity values of agonists at H3 receptors in this preparation.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Taylor SJ,Kilpatrick GJdoi
10.1111/j.1476-5381.1992.tb09036.xsubject
Has Abstractpub_date
1992-03-01 00:00:00pages
667-74issue
3eissn
0007-1188issn
1476-5381journal_volume
105pub_type
杂志文章abstract::In this study, the mechanism of nicotine-induced hippocampal acetylcholine (ACh) release in awake, freely moving rats was examined using in vivo microdialysis. Systemic administration of nicotine (0.4 mg kg(-1), s.c.) increased the levels of ACh in hippocampal dialysates. The nicotine-induced hippocampal ACh release w...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702683
更新日期:1999-07-01 00:00:00
abstract::1 The effects of isoprenaline, propranolol and phosphodiesterase inhibitors on (3)H-transmitter overflow elicited by low frequency nerve stimulation were determined in the isolated perfused spleen of the cat.2 (-)-Isoprenaline (0.14, 1.4, and 14 nM) produced a concentration-dependent increase in [(3)H]-transmitter ove...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1978.tb07779.x
更新日期:1978-05-01 00:00:00
abstract:BACKGROUND AND PURPOSE:We recently reported that AAV1-Rheb(S16H) transduction could protect hippocampal neurons through the induction of brain-derived neurotrophic factor (BDNF) in the rat hippocampus in vivo. It is still unclear how neuronal BDNF produced by AAV1-Rheb(S16H) transduction induces neuroprotective effects...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.14882
更新日期:2020-02-01 00:00:00
abstract::1. The present work describes the effects of inhibitors (amiloride and ethylisopropylamiloride) and activators (quinoxaline and phenylephrine) of the Na(+)-H+ exchanger on the outflow of dopamine in rat kidney slices loaded with L-dihydroxyphenylalanine (L-DOPA). 2. Incubation of kidney slices loaded with 50 microM L-...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1993.tb13608.x
更新日期:1993-06-01 00:00:00
abstract::1. Rat phrenic nerve preparations were used in vitro to study action potential amplitude and nerve conduction time under varying conditions of Pco(2) and sodium bicarbonate concentration in the surrounding Krebs solution.2. A correlation was found between action potential amplitude and pH but not between action potent...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1969.tb07980.x
更新日期:1969-01-01 00:00:00
abstract::1 Endothelin-1 (ET-1), an endothelium-derived vasoactive peptide, participates in the regulation of endothelial function through mechanisms that are not fully elucidated. This study examined the impact of ET-1 on oxidative stress, apoptosis and cell proliferation in human umbilical vein endothelial cells (HUVEC). HUVE...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0706193
更新日期:2005-06-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Recombinant human erythropoietin (rHuEPO) is currently the mainstay of renal anaemia treatment. Recently, rHuEPO has been shown to provide pleiotrophic tissue protection in various pathological conditions. However, the benefits of rHuEPO beyond anaemia treatment are limited because it increases r...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2012.02123.x
更新日期:2013-01-01 00:00:00
abstract::1. Intra-arterial blood pressures and heart rates were recorded in conscious, unrestrained, Long Evans and Brattleboro rats receiving sequential, continuous administrations of selective alpha 1- (prazosin) and alpha 2- (idazoxan) adrenoceptor antagonists. The same protocols were also run in the presence of ICI 118551 ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1988.tb11400.x
更新日期:1988-01-01 00:00:00
abstract::1. The effects of paracetamol and lysine acetylsalicylate (L-AS) on high-threshold mechanonociceptors have been investigated by recording neural activity from the inflamed ankle joint in anaesthetized rats with mild adjuvant-induced monoarthritis. 2. Paracetamol (50 mg kg-1, i.v.) and L-AS (100 mg kg-1, i.v., equivale...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1991.tb12404.x
更新日期:1991-09-01 00:00:00
abstract::1. In cultured endothelial cells of the pig the endothelium-derived relaxing factor (EDRF) releasing agent thrombin (2 u ml-1) caused a significant increase in basal levels of both guanosine 3':5'-cyclic monophosphate (cyclic GMP) and inositol 1,4,5-trisphosphate (IP3). This increase was time dependent, with peak leve...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1991.tb12166.x
更新日期:1991-01-01 00:00:00
abstract::RSD 921 is a novel, structurally unique, class I Na+ channel blocking drug under development as a local anaesthetic agent and possibly for the treatment of cardiac arrhythmias. The effects of RSD 921 on wild-type heart, skeletal muscle, neuronal and non-inactivating IFMQ3 mutant neuronal Na+ channels expressed in Xeno...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702488
更新日期:1999-05-01 00:00:00
abstract:BACKGROUND AND PURPOSE:The non-nucleoside analogue reverse transcriptase inhibitor efavirenz is associated with hepatic toxicity and metabolic disturbances. Although the mechanisms involved are not clear, recent evidence has pinpointed a specific mitochondrial action of efavirenz accompanied by the induction of an endo...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.13018
更新日期:2015-04-01 00:00:00
abstract::1. The effects of tacrine (9-amino-1,2,3,4-tetrahydroacridine), velnacrine (HP029, 9-amino-1,2,3,4-tetrahydroacridin-1-ol maleate), suronacrine (HP128, 9-benzylamino-1,2,3,4-tetrahydroacridin-1-ol maleate), and 3,4-diaminopyridine on neuromuscular transmission were compared on isolated nerve-muscle preparations. 2. Ta...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1991.tb12275.x
更新日期:1991-04-01 00:00:00
abstract:BACKGROUND AND PURPOSE:SU4312, a potent and selective inhibitor of VEGF receptor-2 (VEGFR-2), has been designed to treat cancer. Recent studies have suggested that SU4312 can also be useful in treating neurodegenerative disorders. In this study, we assessed neuroprotection by SU4312 against 1-methyl-4-phenylpyridinium ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.12004
更新日期:2013-03-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Selective and potent antagonists for the β(2) -adrenoceptor are potentially interesting as experimental and clinical tools, and we sought to identify novel ligands with this pharmacology. EXPERIMENTAL APPROACH:A range of pharmacological assays was used to assess potency, affinity, selectivity (β...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2011.01269.x
更新日期:2011-09-01 00:00:00
abstract::Osteoarthritis (OA) is the most common disease of joints, which are complex organs where cartilage, bone and synovium cooperate to allow a range of movements. During progression of the disease, the function of all three main components is jeopardized. Nevertheless, the involvement of each tissue in OA development is s...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bph.14204
更新日期:2019-05-01 00:00:00
abstract::1. Chronic benzodiazepine administration has been associated with tolerance and with downregulation of gamma-aminobutyric acidA (GABAA)-receptor binding and function. However, effects of individual benzodiazepines on brain regions have varied. 2. To compare the effects of chronic lorazepam and alprazolam, we have admi...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1990.tb14167.x
更新日期:1990-12-01 00:00:00
abstract::1. Transepithelial transport of a fluorescent derivative of octreotide (NBD-octreotide) was studied in freshly isolated, functionally intact renal proximal tubules from killifish (Fundulus heteroclitus). 2. Drug accumulation in the tubular lumen was visualized by means of confocal microscopy and was measured by image ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703003
更新日期:2000-01-01 00:00:00
abstract::1. The ability of memantine (1-amino-3,5-dimethyladamantane) to antagonize the modulatory effects of N-methyl-D-aspartate (NMDA) on phosphoinositide turnover stimulated by muscarinic cholinoceptor- and metabotropic glutamate receptor-agonists has been examined in neonatal rat cerebral cortex slices. 2. Memantine antag...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb13275.x
更新日期:1995-02-01 00:00:00
abstract::Serotonin 5-HT(7) receptors are present in astrocytes. Understanding their role in this type of cell would greatly benefit from the identification of astroglial cell lines expressing this receptor type. The aim of the present study was to assess the expression of native 5-HT(7) receptors and 5-HT(7) receptor mRNA in a...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705936
更新日期:2004-10-01 00:00:00
abstract::1 The concept that presynaptic receptors regulate noradrenergic transmitter release via a system of inhibitory receptors mediating negative feedback relies on a supposed association between increases in stimulation-induced efflux of [3H]-noradrenaline by antagonists and blockade by them of the inhibitory effects of ex...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1982.tb09308.x
更新日期:1982-10-01 00:00:00
abstract::Two splice isoforms of rabbit alpha(1a)-adrenergic receptor (AR), (named alpha(1a)-OCU.2-AR and alpha(1a)-OCU.3-AR) have been isolated from the liver cDNA library in addition to the previously reported isoform (alpha(1a)-OCU.1-AR). Although they have the identical splice position with human alpha(1a)-AR isoforms, the ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703242
更新日期:2000-04-01 00:00:00
abstract:BACKGROUND AND PURPOSE:A fluorinated derivative (2F-MT-45) of the synthetic μ-opioid receptor agonist MT-45 (1-cyclohexyl-4-(1,2-diphenylethyl)piperazine) was recently identified in a seized illicit tablet. While MT-45 is a Class A drug, banned in a number of countries, nothing is known about the pharmacology of 2F-MT-...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.15064
更新日期:2020-08-01 00:00:00
abstract::1. We have determined which cytokines induce and modulate the production of the chemokine interleukin-8 (IL-8) by the human colonic epithelial cell line HT-29. 2. Growth arrested cell cultures were stimulated with the human recombinant cytokines interleukin-1 alpha (IL-1 alpha), tumour necrosis factor-alpha (TNF-alpha...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb15993.x
更新日期:1996-09-01 00:00:00
abstract::1. The role of vasoconstrictor 5-HT1-like receptors in the control of vascular reactivity in vivo has been relatively little studied, particularly with regards to venous function. Using an anaesthetized dog model, we have investigated the haemodynamic profile of the selective 5-HT1-like agonist, sumatriptan, focussing...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb15055.x
更新日期:1995-10-01 00:00:00
abstract::1. The endothelial modulation of the relaxant responses to the nitric oxide (NO) donor sodium nitroprusside (SNP) and the KATP channel opener levcromakalim (LEM) and the interactions between these agents were analysed in isolated rat aorta. 2. LEM-induced relaxation was unchanged by endothelium removal or by the prese...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702924
更新日期:1999-12-01 00:00:00
abstract::Cellular electrophysiological effects of membrane lipid peroxidation by t-butyl hydroperoxide (TBH) were studied in the rabbit sinoatrial (SA) node. Superfusion for 1-5 min with 300 microM TBH caused an initial increase and subsequent decrease in the spontaneous firing frequency of the SA node. Voltage clamp experimen...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1989.tb14598.x
更新日期:1989-11-01 00:00:00
abstract::In the present study we used a bioassay to study the effects of peroxynitrite (ONOO-) on angiotensin II (A-II)-triggered tension in isolated bovine coronary arteries in order to show the consequences of the previously reported PGI2-synthase inhibition by ONOO- in this model. The following results were obtained: 1. 1 m...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702434
更新日期:1999-03-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Small conductance calcium-activated potassium (KCa 2.x) channels have a widely accepted canonical function in regulating cellular excitability. In this study, we address a potential non-canonical function of KCa 2.x channels in breast cancer cell survival, using in vitro models. EXPERIMENTAL APP...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.13357
更新日期:2016-01-01 00:00:00
abstract::1. Cold storage (2 degrees C) treatment progressively reduced noradrenaline uptake by the taenia caecum of the guinea-pig. After 15 days of cold treatment, [(3)H]-noradrenaline uptake by tissue was reduced to about 10% of control. On the other hand, prolonged cold storage failed to decrease [(3)H]-adenosine uptake by ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1973.tb08539.x
更新日期:1973-12-01 00:00:00