Abstract：
:1. N(G)-monomethyl-L-arginine (L-NMMA) constricts human forearm resistance vasculature and selectively attenuates vasodilator responses to endothelium-dependent vasodilators. Incomplete inhibition of such responses could be due to an inadequate dose of L-NMMA or to NO-independent vasodilator mechanisms. 2. This study sought to determine doses of L-NMMA that are maximally effective in reducing basal and stimulated forearm blood flow. Drugs were infused via the brachial artery in 32 healthy men. Acetylcholine (11 - 330 nmol min(-1)) was compared with albuterol (0.33 - 10 nmol min(-1)), and nitroprusside (1.7 - 20 nmol min(-1)). 3. The effect of L-NMMA on basal flow approached maximum (53+/-2% reduction) at a dose of 16 micromol min(-1). L-NMMA (16 micromol min(-1)) did not significantly influence responses to nitroprusside, but antagonized acetylcholine and albuterol (each P<0.001, by repeated measures analysis of variance). 4. Inhibition of acetylcholine by L-NMMA (16 micromol min(-1)) was strongly influenced by acetylcholine dose (73+/-7% inhibition at 11 nmol min(-1), P<0.01; 4+/-11% inhibition at 330 nmol min(-1), P=NS, Student's paired t-test). Significant inhibition of albuterol was observed at all doses. 5. A higher dose of L-NMMA (64 micromol min(-1)) did not significantly inhibit the response to acetylcholine (330 nmol min(-1)). Responses to this dose of acetylcholine were unaffected by a cyclo-oxygenase (COX) inhibitor (indometacin) alone but combined COX and NO inhibition attenuated acetylcholine responses by 42+/-19%, implying that there is a compensatory increase in the contribution of prostaglandins or NO to acetylcholine-induced dilatation when one or other pathway is inhibited.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Dawes M,Chowienczyk PJ,Ritter JMdoi
10.1038/sj.bjp.0704338subject
Has Abstractpub_date
2001-11-01 00:00:00pages
939-44issue
5eissn
0007-1188issn
1476-5381journal_volume
134pub_type
临床试验,杂志文章abstract：:Midbrain dopaminergic (DA) neurones sustain important physiological functions such as control of motricity, signalling of the error in prediction of rewards and modulation of emotions and cognition. Moreover, their degeneration leads to Parkinson's disease and they may be dysfunctional in other pathological states, su...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1038/sj.bjp.0706328
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abstract：:1 Eleven analogues of sodium cromoglycate have been tested for their ability to suppress histamine release induced by anti-IgE from passively sensitized human lung fragments in vitro. 2 With the exception of WY 16922, which released histamine at high concentrations, all inhibited histamine release in a linear dose-rel...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1980.tb07937.x
更新日期：1980-10-01 00:00:00
abstract：:1. Isolated preparations of rat anococcygeus muscle were incubated with [3H]-noradrenaline and the efflux of radioactivity induced by stimulation of intramural sympathetic nerves was used as a measure of release of transmitter noradrenaline. Isometric contractile responses were also measured. 2. Angiotensin I (0.03 mi...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1988.tb11657.x
更新日期：1988-10-01 00:00:00
abstract：:The novel urotensin-II (U-II) receptor (UT) ligand, [Pen(5),DTrp(7),Dab(8)]U-II(4-11) (UFP-803), was pharmacologically evaluated and compared with urantide in in vitro and in vivo assays. In the rat isolated aorta, UFP-803 was inactive alone but, concentration dependently, displaced the contractile response to U-II to...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0706438
更新日期：2006-01-01 00:00:00
abstract：:1. We have characterized the human smooth muscle endothelin converting enzyme (ECE) present in the media of the endothelium-denuded human umbilical vein preparation. 2. Endothelin-1 (ET-1) and ET-2 were potent constrictors of umbilical vein with EC50 values of 9.2 nM and 29.6 nM, respectively. ET-1 was at least 30 tim...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701564
更新日期：1997-12-01 00:00:00
abstract：:1. Pithed rats were respired at a fixed rate of 54 cycles min-1 and with a ventilation volume of either 20 (control) or 10 ml kg-1. In these two preparations, the dose-response relationships for the systemic blood pressure responses to endothelin-1, administered i.v., were examined. Also, cardiac output, its distribut...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1989.tb14638.x
更新日期：1989-11-01 00:00:00
abstract：:1. Tyrosine kinases have been proposed as regulators of voltage-operated calcium channels. The effects of a range of structurally different inhibitors of protein tyrosine kinases (PTK) were examined on voltage-operated calcium channel currents (I(Ba)) and pp60(c-src) kinase (c-src) activity in vitro. 2. I(Ba) was meas...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0703186
更新日期：2000-04-01 00:00:00
abstract：:1. Bradykinin has multiple effects on differentiated NG108-15 neuroblastoma x glioma cells: it increases Ins(1,4,5)P3 production and intracellular Ca2+ concentration [Ca2+]i evokes a Ca2+ activated K+ current (IK(Ca)) and inhibits M current (IM). We studied the effect of the aminosteroid U73122 and the antibiotic neom...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0700991
更新日期：1997-03-01 00:00:00
abstract：:1. We showed earlier that NO inhibition caused a left-shift and augmented Emax of the concentration-response curve of AT1-mediated (angiotensin II)-induced vasoconstrictions (AII-VC) in the rat kidney. The 0.01-0.1 nM AII-VC unmasked by the potentiating effect of NO inhibition, were sensitive not only to AT1 (L158809)...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701906
更新日期：1998-07-01 00:00:00
abstract：BACKGROUND AND PURPOSE:A non-psychoactive phytocannabinoid, cannabidiol (CBD), shows promising results as an effective potential antiepileptic drug in some forms of refractory epilepsy. To elucidate the mechanisms by which CBD exerts its anti-seizure effects, we investigated its effects at synaptic connections and on t...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.14202
更新日期：2018-06-01 00:00:00
abstract：:Optimum assay conditions for the association of [3H]-para-tyramine [( 3H]-pTA) with rat brain membranes were characterized, and a saturable, reversible, drug-specific, and high affinity binding mechanism for this trace amine was revealed. The binding capacity (Bmax) for [3H]-pTA in the corpus striatum was approximatel...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1986.tb11116.x
更新日期：1986-09-01 00:00:00
abstract：BACKGROUND AND PURPOSE:The sonic hedgehog pathway (Shh) plays a central role in maintaining stem cell function and behaviour in various processes related to self-renewal and tissue regeneration. However, the therapeutic effect of Shh on mouse embryonic stem cells (mESCs) has not yet been clearly elucidated. Thus, we in...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.14423
更新日期：2018-09-01 00:00:00
abstract：:1. The effect of purified crotapotin, a non-toxic non-enzymatic chaperon protein normally complexed to a phospholipase A2 (PLA2) in South America rattlesnake venom, was studied in the acute inflammatory response induced by carrageenin (1 mg/paw), compound 48/80 (3 micrograms/paw) and 5-hydroxytryptamine (5-HT) (3 micr...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1995.tb17178.x
更新日期：1995-02-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.12225
更新日期：2013-07-01 00:00:00
abstract：:1. Effects of morphine sulphate (1.25, 2.5, 5, 10, 20 and 40 mg/kg i.p.) on locomotor activity of male rats were observed for 8 h after single doses in non-tolerant rats. The lower three doses had only an excitatory effect, whereas the higher three doses caused initial depression followed by a delayed excitatory effec...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1972.tb06866.x
更新日期：1972-10-01 00:00:00
abstract：:1. The fall in arterial blood pressure with bradycardia that occurs on injection of clonidine into the cerebral ventricles and into the cisterna magna is attributed to an action on ;chemosensitive zones' situated at the ventral surface of the brain stem. This conclusion is based on the following results obtained in ca...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1973.tb08532.x
更新日期：1973-12-01 00:00:00
abstract：:Class A1 scavenger receptors (SR-A1) are membrane glycoproteins that can form homotrimers. This receptor was originally defined by its ability to mediate the accumulation of lipids in macrophages. Subsequent studies reveal that SR-A1 plays critical roles in innate immunity, cell apoptosis and proliferation. This revie...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.13105
更新日期：2015-12-01 00:00:00
abstract：:1. Short-circuit current (SCC) technique was used to study the adrenoceptors involved in the electrogenic chloride secretion by cultured cauda epididymal epithelium of rats. Stimulation of the epithelium with noradrenaline (primarily beta 1-adrenoceptor selective agonist), salbutamol (beta 2-adrenoceptor selective ago...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1992.tb14477.x
更新日期：1992-09-01 00:00:00
abstract：:1. Histamine and carbachol produced concentration-related increases in the accumulation of 3H-inositol phosphates in slices of bovine tracheal smooth muscle. 2. Noradrenaline alone produced a small stimulation of 3H-inositol phosphate accumulation which was inhibited by the alpha-adrenoceptor antagonist phentolamine. ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1988.tb11757.x
更新日期：1988-12-01 00:00:00
abstract：:The complement system plays a major role in threat recognition and in orchestrating responses to microbial intruders and accumulating debris. This immune surveillance is largely driven by lectins that sense carbohydrate signatures on foreign, diseased and healthy host cells and act as complement activators, regulators...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.15307
更新日期：2020-11-03 00:00:00
abstract：:1. Piperazinylindoles (DPI 201-106, BDF 8784), drugs known to act on voltage-dependent Na(+)-channels, bind with very high affinity to a Ca2(+)-channel-associated phenylalkylamine receptor in Drosophila melanogaster head membranes. These compounds and (+)-tetrandrine, a naturally occurring Ca2(+)-antagonist, were the ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1991.tb12193.x
更新日期：1991-02-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Cultured pre-adipocytes accumulate and metabolize zidovudine (ZDV), but its mode of accumulation into these cells is unclear. We investigated the mode of accumulation of [(3)H]-ZDV, and the impact of changes in external pH and modulators of drug transporters on its accumulation and metabolism. E...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2009.00552.x
更新日期：2010-01-01 00:00:00
abstract：:1. LP-805, 8-tert-butyl-6,7-dihydropyrrolo-[3,2-e]-5-methylpyrazolo- [1,5a]-pyrimidine-3-carbonitrile, is a newly synthesized potent vasodilator. To investigate the cellular mechanisms of vasorelaxation induced by LP-805, we simultaneously determined the effects of LP-805 on cytosolic Ca2+ concentrations ([Ca2+]i) and...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1994.tb17121.x
更新日期：1994-12-01 00:00:00
abstract：:1. The pharmacological profile of LR-B/081, (methyl 2-[[4-butyl-2-methyl- 6-oxo-5-[[2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]-1(6H)- pyrimidinyl]methyl]-3-thiophenecarboxylate), a novel antagonist at the angiotensin II (AII) AT1-receptor, was studied in vitro and in vivo. 2. In rabbit aortic strips incubated w...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1995.tb13323.x
更新日期：1995-03-01 00:00:00
abstract：:Two prostaglandin endoperoxide analogues, EP 035 and EP 157, behave as specific thromboxane receptor antagonists on isolated smooth muscle preparations such as rabbit aorta, dog saphenous vein and guinea-pig trachea. However, in human platelet-rich plasma (PRP) they produce an unsurmountable block of aggregation induc...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1986.tb10196.x
更新日期：1986-03-01 00:00:00
abstract：:1. Stimulation of the murine macrophage cell line RAW 264.7 with thapsigargin, an endomembrane Ca(2+)-ATPase inhibitor, induced histamine production in a time- and concentration-dependent manner. 2. The protein kinase C activator, 12-O-tetradecanoylphorbol 13-acetate (TPA), also enhanced histamine production. 3. alpha...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0703085
更新日期：2000-02-01 00:00:00
abstract：:1. Action potentials from guinea-pig single ventricular myocytes were interrupted by application of a 300 ms voltage clamp to -40 mV in order to evoke the Ca-activated tail current which is thought to be carried by Na:Ca exchange. Stimulation frequency was 1 Hz and temperature 36 degrees C. 2. The actions of ryanodine...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1990.tb12721.x
更新日期：1990-10-01 00:00:00
abstract：BACKGROUND AND PURPOSE:N-type voltage-gated calcium (Cav 2.2) channels are critical determinants of increased neuronal excitability and neurotransmission accompanying persistent neuropathic pain. Although Cav 2.2 channel antagonists are recommended as first-line treatment for neuropathic pain, calcium-current blocking ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.13737
更新日期：2018-06-01 00:00:00
abstract：:1. The sinus node inhibitors UL FS 49 and DK-AH 269 reduce heart rate by slowing diastolic depolarization rate in the sino-atrial (SA) node, which might originate from the use-dependent blockade of a hyperpolarization-activated current If. A hyperpolarization-activated current Ih, which is present in many types of neu...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702153
更新日期：1998-10-01 00:00:00
abstract：:Antigen challenge in vivo of rat peritoneal cells (enriched with monocytes and polymorphonuclear leucocytes) passively sensitized 2 h previously with homologous antibody of the IgGa class released large amounts of slow-reacting substance of anaphylaxis (SRS-A, 1739 +/- 59 u/ml) into the peritoneal fluid. This reaction...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1977.tb07564.x
更新日期：1977-12-01 00:00:00
