Abstract:
:The hypothesis of negative feedback regulation of noradrenaline release was studied in guinea-pig left atrial halves mounted in vitro. Tissues were transmurally stimulated with 30, 100 or 300 pulses at 2 Hz with pulse durations ranging from 50 mus to 2,000 mus, and the efflux of 3H-transmitter determined. The efflux of tritium increased with increasing pulse duration as was anticipated, but the effects of supposed presynaptic antagonism by yohimbine were opposite to expectations for a negative feedback system. The magnification of efflux by yohimbine, compared to untreated controls was less rather than more as stimulation-induced transmitter efflux climbed with increases in pulse duration, and with all other parameters of stimulation held constant. It is concluded that the neuronal effect of yohimbine is not linked to negative feedback or to any other system sensing the perineuronal concentration of previously released transmitter. Analysis of the effects on tritium efflux of yohimbine and of prolongation of the stimulation pulse duration, reveals a similarity in the way that they promote transmitter release. Yohimbine increased efflux to approximately the same value at all pulse durations between 50 and 1,000 mus and the value reached was equivalent to that obtained in untreated atria during stimulation with very long pulses (2,000 mus duration). It is suggested that yohimbine prolongs the outward current attributable to the efflux of potassium from axon terminals, and by this means prolongs depolarization and the period of transmitter release. Tetraethylammonium (TEA), a quaternary ion known to plug potassium efflux channels, had an effect on transmitter efflux that was, in some ways, similar to that of yohimbine but of greater magnitude. The present findings provide, for the first time, an alternative to the hypothesis of negative feedback, that might explain the presynaptic effects of adrenoceptor antagonists and possibly other compounds.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Kalsner Sdoi
10.1111/j.1476-5381.1983.tb10545.xsubject
Has Abstractpub_date
1983-08-01 00:00:00pages
985-92issue
4eissn
0007-1188issn
1476-5381journal_volume
79pub_type
杂志文章abstract::1. The intravenous infusion of I.C.I. 50172 in doses up to 20 mg reduced, although not significantly, the increase in heart rate produced by the infusion of isoprenaline in healthy volunteers; the response to adrenaline was significantly reduced. The infusion of 1 mg propranolol abolished these responses2. After the p...
journal_title:British journal of pharmacology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1476-5381.1968.tb07956.x
更新日期:1968-09-01 00:00:00
abstract::Some 865 genes in man encode G-protein-coupled receptors (GPCRs). The heterotrimeric guanine nucleotide-binding proteins (G-proteins) function to transduce signals from this vast panoply of receptors to effector systems including ion channels and enzymes that alter the rate of production, release or degradation of int...
journal_title:British journal of pharmacology
pub_type: 历史文章,杂志文章,评审
doi:10.1038/sj.bjp.0706405
更新日期:2006-01-01 00:00:00
abstract::The platelet-lowering drug anagrelide inhibits bone marrow megakaryocytopoiesis by an unknown mechanism. Recently, it was found that anagrelide is bio-transformed in humans into two major metabolites (6,7-dichloro-3-hydroxy-1,5 dihydro-imidazo[2,1-b]quinazolin-2-one (BCH24426) and 2-amino-5,6-dichloro-3,4,-dihydroquin...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0706341
更新日期:2005-10-01 00:00:00
abstract::1. Several amino-acid esters and amides have been prepared and their toxicological and pharmacological properties have been investigated. Some of the quaternary esters and amides were lethal to mice at doses below 1 mg/kg; this lethality was usually associated with high nicotinic activity. None of the compounds showed...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1968.tb07056.x
更新日期:1968-10-01 00:00:00
abstract::1,1-Azobis[3-methyl-2-phenylbenzimidazolinium]dimethanesulphonate (AH 10407) has an ultrashort, competitive neuromuscular blocking action in the mouse, cat, dog, Cynamolgus monkey and cotton-eared marmoset. 2 AH 10407 is chemically unstable in bicarbonate-containing solutions and is degraded to inactive products. The ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1977.tb09738.x
更新日期:1977-09-01 00:00:00
abstract::The ability of beta-adrenoceptor agonists to reduce the fusion of incomplete tetanic contractions of the soleus muscle of the cat has been used previously as a model to assess the potential tremor producing effect of sympathomimetic bronchodilators. The ability of (-)-isoprenaline, (-)-adrenaline, (+/-)-soterenol and ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1972.tb07297.x
更新日期:1972-03-01 00:00:00
abstract::1. The effects of forskolin, a direct activator of adenylate cyclase and sodium nitroprusside, a direct activator of guanylate cyclase, were studied on rabbit isolated ear arteries preconstricted with 80 mM potassium. 2. Bolus injection of these two compounds resulted in vasodilatation. They had similar potencies in t...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1989.tb11873.x
更新日期:1989-03-01 00:00:00
abstract::1. We investigated the cytoprotective effect of low-dose nitric oxide (NO) on NO-induced cell death in mouse macrophage-like cell line RAW264. 2. Sodium nitroprusside (SNP), an NO donor, at a high concentration (4 mM) released cytochrome c from mitochondria and induced death in RAW264 cells. Acetyl-L-aspartyl-L-glutam...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705206
更新日期:2003-05-01 00:00:00
abstract::The effects of pretreatment with 16,16-dimethyl prostaglandin E2 (DmPGE2) on the recovery of gastric mucosal 'barrier' parameters after ethanol-induced damage were studied using an ex vivo chamber preparation in the rat. DmPGE2 (4-40 micrograms kg-1) significantly reduced the extent of haemorrhagic damage to the gastr...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1985.tb11105.x
更新日期:1985-12-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Toll-like receptor 4 (TLR4) signalling contributes to inflammatory cardiovascular diseases, but its role in hypertension and the associated vascular damage is not known. We investigated whether TLR4 activation contributed to angiotensin II (AngII)-induced hypertension and the associated vascular ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.13117
更新日期:2015-06-01 00:00:00
abstract::The characteristics of the rat epidydimal adipocyte beta-adrenoceptor have been examined using lipolysis and cyclic AMP accumulation in adipocytes as well as adenylate cyclase activity in fat cell membranes. The pA2 values corrected for binding to bovine serum albumin of the selective antagonists betaxolol (beta 1-sel...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:
更新日期:1985-01-01 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::In anaesthetized dogs at room temperatures of 28-33 degrees C, the cerebral ventricles were perfused with artificial CSF from the left lateral ventricular to the aqueductal cannulae. The animals' temperatures were recorded from the rectum. Addition of Ca(++) in excess to the artificial CSF perfusing the ventricles pro...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1973.tb08547.x
更新日期:1973-12-01 00:00:00
abstract::Spontaneous inhibitory postsynaptic currents (i.p.s.cs) were recorded in voltage-clamped CA1 neurones in rat hippocampal slices. The exponential decay of i.p.s.cs was prolonged by concentrations of sodium pentobarbitone as low as 50 microM. With concentrations up to 100 microM, there was no change in the amplitude or ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1985.tb10563.x
更新日期:1985-07-01 00:00:00
abstract::N-ethylmaleimide (NEM) has been reported to interact with the GTP-binding Ni-protein; we have examined its effect on adenosine receptor binding in feline cortical membranes and on adenosine-receptor mediated effects on cyclic AMP accumulation in rat hippocampal slices. Treatment of cortical membranes with NEM (100 mic...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1985.tb08922.x
更新日期:1985-10-01 00:00:00
abstract::1 Vasoactive intestinal polypeptide (VIP, 0.01- MicroM) produced dose-related relaxations of the mouse anococcygeus muscle. 2 Following incubation with indomethacin (2.8 microM 1 h) adenosine 5'-triphosphate (ATP, 0.5-10 mM) produced dose-related relaxations of the mouse anococcygeus. 3 Haemolysed blood reduced inhibi...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1982.tb09274.x
更新日期:1982-09-01 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. To obtain direct evidence of abnormal eicosanoid biosynthesis in rats injected with anti-glomerular-basement-membrane antibodies (a-GBM), products derived from thromboxane A2 (TXA2) and prostacyclin (PGI2) were measured in 24 h urine collections before and after a-GBM. 2. Administration of a-GBM (9.5 mg) caused alb...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1991.tb09844.x
更新日期:1991-07-01 00:00:00
abstract::1. We have studied whether a nucleotide receptor mediates the effects of extracellular ATP and UTP on phosphatidylcholine metabolism in rat cultured glomerular mesangial cells. 2. ATP and UTP stimulated a biphasic 1,2-diacylglycerol (DAG) formation in [3H]-arachidonic acid-labelled mesangial cells. In contrast, in cel...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1993.tb13890.x
更新日期:1993-10-01 00:00:00
abstract::The properties of the ATPase released during electrical field stimulation (EFS) (8 Hz, 25 s) of the sympathetic nerves of the superfused rabbit isolated vas deferens were investigated. Superfusate collected during EFS rapidly metabolised exogenous ATP (100 microM) and 50% was broken down in 5.67+/-0.65 min. The main m...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703662
更新日期:2000-11-01 00:00:00
abstract::1. This study investigated whether (a) cannabinoid CB(1) receptor knockout (CB(1)(-/-)) mice displayed altered gastrointestinal transit and (b) cannabinoid CB(1) and opioid receptors functionally interact in the regulation of gastrointestinal transit. 2. Gastrointestinal transit was assessed by the Whole Gastrointesti...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0706824
更新日期:2006-08-01 00:00:00
abstract::Injection of carrageenan 1% (50 microl) in the mouse paw causes a biphasic response: an early inflammatory response that lasts 6 h and a second late response that peaks at 72 h, declining at 96 h. Only mice 7- or 8-week old, weighing 32-34 g, displayed a consistent response in both phases. In 8-week-old mice, myeloper...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705650
更新日期:2004-05-01 00:00:00
abstract::1 Rats treated for seven days with seryl-trihydroxybenzylhydrazine (benserazide), and inhibitor of peripheral aromatic L-amino acid decarboxylase (500 mg/kg, daily, i.p.) alone or in combination with L-DOPA methylester (500 mg/kg, daily, i.p.) for seven days showed a moderate but significant decrease of liver aldehyde...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1977.tb16746.x
更新日期:1977-05-01 00:00:00
abstract::1. Noradrenaline sensitivity and acetylcholine-induced relaxation were investigated in mesenteric resistance arteries from female Wistar rats (220-250 g) following exposure to isotonic supraphysiological glucose solutions (20 and 45 mM, in physiological buffer, 2 h incubation). 2. Arteries incubated in 20 mM glucose d...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1994.tb17064.x
更新日期:1994-11-01 00:00:00
abstract:BACKGROUND AND PURPOSE:AZ11645373 and N-{2-methyl-5-[(1R, 5S)-9-oxa-3,7-diazabicyclo[3.3.1]non-3-ylcarbonyl]phenyl}-2-tricyclo[3.3.1.13,7]dec-1-ylacetamide hydrochloride (compound-22) are recently described P2X(7) receptor antagonists. In this study we have further characterized these compounds to determine their mecha...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2009.00135.x
更新日期:2009-04-01 00:00:00
abstract::1 The responses of excitatory junctions on locust skeletal muscle fibres to iontophoretically applied L-glutamic acid and DL-ibotenic acid, a rigidly extended analogue of glutamate, were recorded by means of intracellular microelectrodes.2 Iontophoresis of L-glutamate to junctional sites produced transient depolarizat...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1979.tb13675.x
更新日期:1979-06-01 00:00:00
abstract::1. Cumulative concentration-response curves (CRC) to prostaglandin E1 (PGE1), PGE2, PGD2 and PGF2alpha (0.01-30 microM) and to the thromboxane A2 (TXA2) receptor agonist U-46619 (0.01-30 microM) were constructed in human isolated detrusor muscle strips both in basal conditions and during electrical field stimulation. ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701903
更新日期:1998-07-01 00:00:00
abstract::1. The effects of intracerebroventricular (i.c.v.) and intracisternal (i.c.) administration of corticotrophin releasing factor (CRF) (0.5 nmol kg-1) were examined in conscious rabbits. The effect of opioid receptor antagonism was examined to determine whether the responses to CRF were mediated by endogenous opioid pep...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1991.tb09862.x
更新日期:1991-07-01 00:00:00
abstract::1 The concentrations of p- and m-tyramine were measured in the caudate nucleus of the rat brain following subcutaneous injection of reserpine or intraventricular injection of 6-hydroxydopamine, beta-Phenylethylamine was analysed in the hypothalamus after reserpine. 2 Endogenous levels of p-tyramine and m-tyramine in t...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1977.tb06996.x
更新日期:1977-01-01 00:00:00
abstract::1. Tachycardia and bronchodilatation were produced by intravenous dimethylphenylpiperazinium iodide (DMPP) in the spinal or pithed cat. Responses other than those involving beta-adrenoceptors were minimized by appropriate blocking agents.2. With intact adrenals, both the tachycardia and bronchodilatation with 10 mug/k...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1973.tb08256.x
更新日期:1973-08-01 00:00:00