Abstract:
:1. We investigated the role of nitric oxide (NO) in modulating spinal synaptic responses evoked by electrical and noxious sensory stimuli in the neonatal rat spinal cord in vitro. 2. Potentials were recorded extracellularly from a ventral root (L3-L5) of the isolated spinal cord preparation or spinal cord-saphenous nerve-skin preparation of 0- to 2-day-old rats. Spinal reflexes were elicited by electrical stimulation of the ipsilateral dorsal root or by noxious skin stimulation. 3. In the spinal cord preparation, single shock stimulation of a dorsal root at C-fibre strength induced mono-synaptic reflex followed by a slow depolarizing response lasting about 30 s (slow ventral root potential; slow VRP) in the ipsilateral ventral root of the same segment. Bath-application of NO gas-containing medium (10(-4)- 10(-2) dilution of saturated medium) and NO donors, 1-hydroxy-2-oxo-3-(N-ethyl-2-aminoethyl)-3-ethyl-1-triazene (NOC12, 3-300 microM), S-nitroso-N-acetyl-D,L-penicillamine (SNAP, 3-300 microM) and S-nitroso-L-glutathione (GSNO, 3-300 microM), produced an inhibition of the slow VRP and a depolarization of ventral roots. Another NO donor, 3-morpholinosydononimine (SIN-1, 30-300 microM), also depressed the slow VRP but did not depolarize ventral roots. These agents did not affect the mono-synaptic reflex. 4. In the spinal cord-saphenous nerve-skin preparation, application of capsaicin (0.1-0.2 microM) to skin evoked a slow depolarizing response of the L3 ventral root. This slow VRP was depressed by NOC12 (10-300 microM) and SIN-1 (100-300 microM). When the concentration of NOC12 was increased to 1 mM, spontaneous synaptic activities were augmented and the depressant effect of NOC12 on the slow VRP became less pronounced. 5. A NO-scavenger, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide( carboxy- PTIO, 100-300 microM) prevented the depressant effect on the dorsal root-evoked slow VRP and ventral root depolarizing effects of NO donors. Carboxy-PTIO increased spontaneous synaptic activities and markedly potentiated the slow VRP. A NO synthase (NOS) inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME, 0.03-1 microM), but not D-NAME (0.03-1 microM), also markedly potentiated the slow VRP and this effect was reversed by L-arginine (300 microM). 6. 8-Bromo-cyclic guanosine 3': 5'-monophosphate (8-Br-cyclic GMP, 100-300 microM) produced both an inhibition of the slow VRP and a depolarization of ventral roots. A cyclic GMP-dependent protein kinase inhibitor, KT5823 (0.3 microM), partly inhibited the depressant effects of NO donors and 8-Br-cyclic GMP on the dorsal root-evoked slow VRP. In contrast, KT5823 did not inhibit the depolarizing effects of NO donors. 7. Perfusion of the spinal cord with medium containing tetrodotoxin (0.3 microM) and/or low Ca2+ (0.1 mM)-high Mg2+ (10 mM) markedly potentiated the depolarizing effect of NO donors. The SNAP-evoked depolarization in the tetrodotoxin-containing low Ca(2+)-high Mg2+ medium was significantly inhibited by excitatory amino acid receptor antagonists D-(-)-2-amino-5-phosphonovaleric acid (30 microM) and 6-cyano-7-nitroquinoxaline-2,3-dione (10 microM). 8. The present study suggests that inhibitory and excitatory mechanisms meditated by the NO-cyclic GMP cascade are involved in the primary afferent fibre-evoked nociceptive transmission in the neonatal rat spinal cord. The inhibitory mechanism, but not the excitatory mechanism, appears to be partly mediated by cyclic GMP-dependent protein kinase. It is also suggested that Ca(2+)-independent release of excitatory amino acid neurotransmitters contributes to the depolarizing response to NO of ventral roots.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Kurihara T,Yoshioka Kdoi
10.1111/j.1476-5381.1996.tb15600.xsubject
Has Abstractpub_date
1996-08-01 00:00:00pages
1743-53issue
7eissn
0007-1188issn
1476-5381journal_volume
118pub_type
杂志文章abstract::In this issue, BJP is proud to publish an Endothelium Themed Section to celebrate the life of Robert F. Furchgott, who died on May 19th 2009. It is 30 years since he discovered endothelium-derived relaxant factor and a decade since he was awarded the Nobel Prize for this work. His discovery has led to an array of new ...
journal_title:British journal of pharmacology
pub_type: 社论
doi:10.1111/j.1476-5381.2009.00366.x
更新日期:2009-06-01 00:00:00
abstract::1 The rates at which tubocurarine associates with, and dissociates from, the nicotinic receptor, while exerting its classical competitive effect, are still in doubt. We have investigated this problem by observing the effect of low concentrations of tubocurarine on the re-equilibration rate, following a step change in ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1982.tb08759.x
更新日期:1982-01-01 00:00:00
abstract::1. The kinetics of glycine-sensitive, N-methyl-D-aspartate (NMDA) receptor desensitization were investigated in cultured neurones with the patch clamp technique. 2. The degree of fast NMDA-receptor desensitization was inversely related to glycine concentration. Thus, increasing concentrations of glycine from 30 nM to ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1993.tb13556.x
更新日期:1993-05-01 00:00:00
abstract::1. Previous studies demonstrated that elevation of the extracellular calcium concentration during a prolonged exposure to a high concentration of carbachol reverses the staurosporine-induced decrease in the extent of endplate resensitization in voltage-clamped snake twitch fibres. The present studies were designed to ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1993.tb13896.x
更新日期:1993-10-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Fatty acid amide hydrolase inhibitors show promise as a treatment for anxiety, depression and pain. Here we investigated whether perinatal exposure to URB597, a fatty acid amide hydrolase inhibitor, alters brain development and affects behaviour in adult mice. EXPERIMENTAL APPROACH:Mouse dams we...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.12500
更新日期:2014-03-01 00:00:00
abstract::1. The pharmacokinetics of cyclophosphamide were investigated in cancer patients. The data can be characterized by a two-compartment open model. The half life of the elimination phase of the drug ranged between 3 and 11 hours.2. Extensive tubular reabsorption of the drug resulted in the excretion of only a small perce...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1971.tb07199.x
更新日期:1971-11-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Nitric oxide (NO) is known to activate NO-sensitive guanylyl cyclase (NO-GC) and to elicit cGMP production. However, NO has also been proposed to induce cGMP-independent effects. It is accepted practice to use specific NO-GC inhibitors, such as ODQ or NS2028, to assess cGMP-dependent NO effects. ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.12275
更新日期:2013-09-01 00:00:00
abstract::1. The convulsive effects of leptazol in the rat are potentiated by prior treatment with dexamphetamine.2. An intact dopamine synthesis is necessary for the potentiation of the convulsive action of leptazol.3. An intact noradrenaline synthesis is not necessary for this action of amphetamine, as long as the dopamine sy...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1969.tb09526.x
更新日期:1969-09-01 00:00:00
abstract::1. Block by philanthotoxin-343 (PhTX-343), a neurotoxin from wasps, of ionic currents mediated through neuronal nicotinic acetylcholine (ACh) receptor/channels was characterized in rat phaeochromocytoma PC12 cells, by use of whole cell voltage-clamp techniques. 2. In the cells held at -60 mV, PhTX-343 at 0.1 and 1 mic...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701373
更新日期:1997-09-01 00:00:00
abstract::1. Juvenile male rats treated with parachlorophenylalanine showed hair loss round the head and neck extending down the chest and abdomen.2. Treated isolated rats did not have this loss of hair, while untreated animals living in the same cage as treated rats lost their hair. The loss therefore seems to be caused by inc...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1970.tb08518.x
更新日期:1970-02-01 00:00:00
abstract::1 Tissue was taken from guinea-pigs that had been injected with guanethidine (100 mg/kg, i.p.) 24 h before they were killed, and from paired control animals.2 Pretreatment with guanethidine caused a significant, substantial, and sometimes complete reduction of the nerve-mediated contractions of the vas deferens. There...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1974.tb09593.x
更新日期:1974-01-01 00:00:00
abstract::1. We have previously shown that 11-keto boswellic acids (11-keto-BAs), the active principles of Boswellia serrata gum resins, activate p38 MAPK and p42/44(MAPK) and stimulate Ca(2+) mobilisation in human polymorphonuclear leucocytes (PMNL). 2. In this study, we attempted to connect the activation of MAPK and mobilisa...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705604
更新日期:2004-01-01 00:00:00
abstract::Preclinical and clinical data suggest that a modification in GABA(B) receptor expression and function may contribute to the symptoms of major depression and the response to antidepressants. This includes laboratory animal experiments demonstrating that antidepressants modify brain GABA(B) receptor expression and funct...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1476-5381.2010.01004.x
更新日期:2011-01-01 00:00:00
abstract::1. The aim of the study was to investigate the mechanism of a novel effect of hypoxia on intracellular Ca(2+) signalling in rabbit cerebral arteriolar smooth muscle cells, an effect that was resistant to the L-type Ca(2+) channel antagonist methoxyverapamil (D600). 2.[Ca(2+)](i) of smooth muscle cells in intact arteri...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704547
更新日期:2002-02-01 00:00:00
abstract::1. We have shown earlier that pilocarpine strongly inhibits mouse and human liver coumarin 7-hydroxylase activity of CYP 2A and pentoxyresorufin O-deethylase activity of CYP 2B in vitro. Since pilocarpine, like coumarin, contains a lactone structure we have studied in more detail its inhibitory potency on mouse and hu...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb17217.x
更新日期:1995-11-01 00:00:00
abstract::Eotaxin is a novel C-C chemokine with selective chemoattractant activity for eosinophils. We determined whether eotaxin could be produced by human airway smooth muscle (HASM) cells in culture and examined its regulation by interleukin-10 (IL-10) and the corticosteroid, dexamethasone. Stimulation of the cells with inte...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702660
更新日期:1999-07-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Amitriptyline is often prescribed as a first-line treatment for neuropathic pain but its precise mode of analgesic action remains uncertain. Amitriptyline is known to inhibit voltage-dependent ion channels and also to act as an antagonist at ligand-gated ion channels, such as nicotinic acetylchol...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2009.00347.x
更新日期:2009-10-01 00:00:00
abstract::The past two decades have seen an immense increase in our appreciation of the vast range of signalling processes and supporting machinery that occur in cells. Pivotal to this is the notion of signal compartmentalization (compartmentation). Targeting by protein domains is critical in allowing signalling complexes to be...
journal_title:British journal of pharmacology
pub_type: 评论,杂志文章
doi:10.1111/j.1476-5381.2009.00359.x
更新日期:2009-09-01 00:00:00
abstract::Muscularis mucosa of the distal oesophagus of the opossum contains nerves which release acetylcholine and substance P(SP)-like material on field stimulation. The release of SP-like material appeared to be inhibited by the presence of exogenous muscarinic agonists and potentiated by muscarinic antagonists. Analysis of ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1986.tb10254.x
更新日期:1986-07-01 00:00:00
abstract::1. The relaxant effects of Zeneca ZD7114, BRL37344 (putative beta 3-adrenoceptor agonists) and various phenylethylamine-based agonists were studied in isolated ileum of the rat where tone was increased with carbachol (0.5 microM). Agonist-induced relaxation.was measured under equilibrium conditions with alpha-, beta 1...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1993.tb13972.x
更新日期:1993-12-01 00:00:00
abstract::1. Catecholamine release from cat adrenal glands perfused at a high rate (4 ml min-1) at 37 degrees C with modified Krebs solutions lacking Ca and containing 1.2 mM K (hyperpolarizing solution) or 118 mM K (depolarizing solution) was triggered by 10-s pulses of Ca (0.5 mM) in the presence of 118 mM K. Hyperpolarized g...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1989.tb11874.x
更新日期:1989-03-01 00:00:00
abstract::Null equations have been derived which, when applied to log10 concentration-tissue state curves for an agonist determined in the presence and absence of a competitive antagonist which also exhibits functional interaction, allow quantitation of the characteristics of the competitive and functional interactant effects. ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1985.tb08856.x
更新日期:1985-05-01 00:00:00
abstract::1. The effects of purinergic stimulation on action potential, force of contraction, 86Rb efflux and 45Ca uptake were investigated in guinea-pig left atria. 2. Adenosine exerted a negative inotropic effect which was antagonized by adenosine deaminase but enhanced by dipyridamole. 3. The negative inotropic effect of ade...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1989.tb12577.x
更新日期:1989-08-01 00:00:00
abstract::The histamine H3 receptor, first described in 1983 as a histamine autoreceptor and later shown to also function as a heteroreceptor that regulates the release of other neurotransmitters, has been the focus of research by numerous laboratories as it represents an attractive drug target for a number of indications inclu...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1038/bjp.2008.147
更新日期:2008-07-01 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::1. The release of prostaglandin D2 (PGD2) during immediate allergic reactions in human skin was investigated in vivo and in vitro. 2. Skin exudates were collected from abraded sites on the thigh of atopic subjects sensitive to D. pteronyssinus antigen and from non-atopic control subjects. Challenge with antigen caused...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1988.tb11588.x
更新日期:1988-07-01 00:00:00
abstract::The effects of dopamine receptor and alpha-adrenoceptor agonists and antagonists on the stimulation-evoked overflow of radioactivity from strips of dog saphenous vein previously loaded with [3H]-noradrenaline have been examined alone and in combination. In the presence of neuronal and extraneuronal catecholamine uptak...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1984.tb10098.x
更新日期:1984-03-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Agmatine, a putative neurotransmitter, plays a vital role in learning and memory. Although it is considered an endogenous ligand of imidazoline receptors, agmatine exhibits high affinity for α-adrenoceptors, NOS and NMDA receptors. These substrates within the locus coeruleus (LC) are critically i...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.13531
更新日期:2016-09-01 00:00:00
abstract::The fate and activity of drugs are frequently dictated not only by the host per se but also by the microorganisms present in the gastrointestinal tract. The gut microbiome is known to, both directly and indirectly, affect drug metabolism. More evidence now hints at the effects that drugs can have on the function and c...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bph.14366
更新日期:2018-12-01 00:00:00
abstract:BACKGROUND AND PURPOSE:The aim of this study was to identify the actions of H(2)S on ion transport across rat distal colon. EXPERIMENTAL APPROACH:Changes in short-circuit current (Isc) induced by the H(2)S-donor, NaHS, were measured in Ussing chambers. Cytosolic Ca(2+) concentration was evaluated using fura-2. KEY RE...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2009.00385.x
更新日期:2009-11-01 00:00:00