Abstract:
:1. The interactive effects of different metabotropic glutamate (mGlu) receptor subtypes to regulate phosphoinositide turnover have been studied in neonatal rat cerebral cortex and hippocampus by use of agonists and antagonists selective between group I and II mGlu receptors. 2, The group II-selective agonist 2R,4R-4-aminopyrrolidine-2,4-dicarboxylate (2R,4R-APDC; 100 microM) had no effect on basal total inositol phosphate ([3H]-InsPx) accumulation (in the presence of Li+) in myo-[3H]-inositol pre-labelled slices, but enhanced the maximal [3H]-InsPx response to the group I-selective agonist (S)-3,5-dihydroxyphenylglycine (DHPG) by about 100% in both hippocampus and cerebral cortex. In cerebral cortex the enhancing effect of 2R,4R-APDC occurred with respect to the maximal responsiveness and had no effect on EC50 values for DHPG (-log EC50 (M): control, 5.56+/-0.05; +2R,4R-APDC, 5.51+/-0.08). 2R,4R-APDC also caused a significant enhancement of the DHPG-stimulated inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) mass response over an initial 0-300 s time-course. 3. The enhancing effects of 2R,4R-APDC on DHPG-stimulated [3H]-InsPx accumulation were observed in both the presence and nominal absence of extracellular Ca2+, and irrespective of whether 2R,4R-APDC was added before, simultaneous with, or subsequent to DHPG. Furthermore, increasing the tissue cyclic AMP concentration up to 100 fold had no effect on DHPG-stimulated Ins(l,4,5)P3 accumulation in the absence or presence of 2R,4R-APDC. 4. 2R,4R-APDC and (2S, 1'R, 2'R, 3'R)-2-(2,3-dicarboxylcyclopropyl)glycine (DCG-IV), the latter agent in the presence of MK-801 to prevent activation of NMDA-receptors, each inhibited forskolin-stimulated cyclic AMP accumulation by about 50%, with respective EC50 values of 1.3 and 0.04 microM (-log EC 50 (M): 2R,4R-APDC, 5.87+/-0.09; DCG-IV, 7.38+/-0.05). In the presence of DHPG (30 microM), 2R,4R-APDC and DCG-IV also concentration-dependently increased [3H]-InsPx accumulation with respective EC50 values of 4.7 and 0.28 microM (-log EC50 (M): 2R,4R-APDC, 5.33+/-0.04; DCG-IV, 6.55+/-0.09) which were 3-7 fold rightward-shifted relative to the adenylyl cyclase inhibitory responses. 5. The group II-selective mGlu receptor antagonist LY307452 (30 microM) caused parallel rightward shifts in the concentration-effect curves for inhibition of forskolin-stimulated adenylyl cyclase, and enhancement of DHPG-stimulated [3H]-InsPx accumulation, by 2R,4R-APDC yielding similar equilibrium dissociation constants (KdS, 3.7+/-1.1 and 4.1+/-0.4 microM respectively) for each response. 6. The ability of 2R,4R-APDC to enhance receptor-mediated [3H]-InsPx accumulation appeared to be agonist-specific; thus although DHPG (100 microM) and the muscarinic cholinoceptor agonist carbachol (10 microM) stimulated similar [3H]-InsPx accumulations, only the response to the former agonist was enhanced by co-activation of group II mGlu receptors. 7. These data demonstrate that second messenger-generating phosphoinositide responses stimulated by group I mGlu receptors are positively modulated by co-activation of group II mGlu receptors in cerebral cortex and hippocampus. The data presented here are discussed with respect to the possible mechanisms which might mediate the modulatory activity, and the physiological and pathophysiological significance of such crosstalk between mGlu receptors.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Mistry R,Golding N,Challiss RAdoi
10.1038/sj.bjp.0701626subject
Has Abstractpub_date
1998-02-01 00:00:00pages
581-9issue
3eissn
0007-1188issn
1476-5381journal_volume
123pub_type
杂志文章abstract::1. 2-2' Pyridylisatogen tosylate (PIT) (greater than 2.5 muM) relaxed the guinea-pig isolated taenia caeci by an unknown mechanism. 2. With higher concentrations of PIT (greater than 12.5 muM) subsequent applications of adenosine 5'-triphosphate (ATP) (2-600 muM) revealed a blockade of the ATP receptors. The antagonis...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1975.tb07397.x
更新日期:1975-04-01 00:00:00
abstract:BACKGROUND AND PURPOSE:As a hallmark of glioblastoma multiforme (GBM), CD44 plays a crucial role in promoting glioblastoma stem cell (GSC) stemness phenotypes and multiple drug resistance. The therapeutic potential of CD44 has been validated by the clinical successes of several CD44 inhibitors, including antibodies and...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.15030
更新日期:2020-07-01 00:00:00
abstract::1. Reserpine given to rats before the enhanced synthesis of DNA begins 14h after partial hepatectomy markedly depresses thymidine uptake into DNA at 24 hours.2. At this time decreased activity of liver thymidine kinase but unchanged thymidine 5'-nucleotidase were observed.3. Reserpine has no effect on DNA synthesis wh...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1973.tb08370.x
更新日期:1973-10-01 00:00:00
abstract:BACKGROUND AND PURPOSE:The adenosine 2B (A2B) receptor is the predominant adenosine receptor expressed in the colon. Acting through the A2B receptor, adenosine mediates chloride secretion, as well as fibronectin and interleukin (IL)-6 synthesis and secretion in intestinal epithelial cells. A2B receptor mRNA and protein...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/bjp.2008.227
更新日期:2008-09-01 00:00:00
abstract::1. The effects of the putative gap junction uncoupler, 1-heptanol, on the neurogenic and myogenic contractile responses of guinea-pig vas deferens were studied in vitro. 2. Superfusion of 2.0 mM heptanol for 20-30 min produced the following reversible changes in the biphasic neurogenic contractile response (8 trials):...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702307
更新日期:1999-01-01 00:00:00
abstract::1. The effects of some rapidly metabolized sympathomimetic amines, such as beta-phenylethylamine and p-tyramine, in eliciting hypertensive responses to reserpine in the anaesthetized rat, have been studied.2. Retardation of metabolism, by pretreatment with the monoamineoxidase inhibitors iproniazid or phenelzine, caus...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1972.tb07256.x
更新日期:1972-02-01 00:00:00
abstract::1. In many cancer patients, 5-fluorouracil (5-FUra) treatment is toxic and even causes death. Nevertheless, all patients are subjected to a standard therapy regimen because there is no reliable way to identify beforehand those patients who are predisposed to 5-FUra-induced toxicity. In this study, we identified the di...
journal_title:British journal of pharmacology
pub_type: 临床试验,杂志文章
doi:10.1038/sj.bjp.0705651
更新日期:2004-02-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Inhibition of PDE5 improves synaptic plasticity and memory via enhancing cGMP expression, thus activating the cGMP/cAMP response element binding protein (CREB) signalling pathway. This study investigated the effects of a PDE5 inhibitor on scopolamine-induced cognitive dysfunction, using memory-re...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.14377
更新日期:2018-08-01 00:00:00
abstract:BACKGROUND AND PURPOSE:During angiogenesis, quiescent endothelial cells (ECs) are activated by various stimuli to form new blood vessels from pre-existing ones in physiological and pathological conditions. Many research groups have shown that hydrogen sulfide (H2 S), the newest member of the gasotransmitter family, act...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.14574
更新日期:2020-02-01 00:00:00
abstract::1. Murine left atrium lacks inotropic beta(2)-adrenoceptor function. We investigated whether beta(2)-adrenoceptors are involved in the cardiostimulant effects of (-)-adrenaline on spontaneously beating right atria and paced right ventricular myocardium of C57BL6 mice. We also studied a negative inotropic effect of (-)...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704700
更新日期:2002-05-01 00:00:00
abstract::1. Rasagiline [N-propargyl-1R(+)-aminoindan], was examined for its monoamine oxidase (MAO) A and B inhibitor activities in rats together with its S(-)-enantiomer (TVP 1022) and the racemic compound (AGN-1135) and compared to selegiline (1-deprenyl). The tissues that were studied for MAO inhibition were the brain, live...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703826
更新日期:2001-01-01 00:00:00
abstract::The iodine-containing contrast medium iopanoic acid induces alterations of thyroid hormone metabolism comparable to those observed with the iodine-containing antiarrhythmic drug amiodarone. Both compounds inhibit the intracellular conversion of thyroxine (T4) to triiodothyronine (T3). Using iopanoic acid, the question...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1986.tb10217.x
更新日期:1986-06-01 00:00:00
abstract::1 The effect of intrarenal histamine, dimaprit (H2-agonist) and 2-(2-pyridyl) ethylamine (H1-agonist) on renin release was examined in anaesthetized dogs. 2 In dogs with intact kidneys, histamine and dimaprit administration resulted in renal vasodilatation, a two fold increase in urinary sodium excretion, and no chang...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1983.tb10495.x
更新日期:1983-05-01 00:00:00
abstract::1. Bradykinin (BK) and Lys-BK are peptides which are released at high nanomolar concentrations into the tear-film of ocular allergic patients. We hypothesized that these peptides may activate specific receptors on the ocular surface, especially the corneal epithelium (CE) and thus the CE cells may represent a potentia...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701168
更新日期:1997-06-01 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::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:Angiotensin AT1 receptor antagonists induce weight loss; however, the mechanism underlying this phenomenon is unknown. The Mas receptor agonist angiotensin-(1-7) is a metabolite of angiotensin I and of angiotensin II . As an agonist of Mas receptors, angiotensin-(1-7) has beneficial cardiovascula...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.13172
更新日期:2015-08-01 00:00:00
abstract::1. In the present study, we describe the expression of the neuropeptides vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) as well as their receptors in PC-3 cells, a human prostate cancer cell line. In addition, we have investigated their role in apoptosis induced by s...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705317
更新日期:2003-07-01 00:00:00
abstract:UNLABELLED:Sensory neurons play important roles in many disorders, including inflammatory diseases, such as sepsis. Sepsis is a potentially lethal systemic inflammatory reaction to a local bacterial infection, affecting thousands of patients annually. Although associated with a high mortality rate, sepsis outcome depen...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bph.12056
更新日期:2013-12-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Two of the most relevant unmet needs in epilepsy are represented by the development of disease-modifying drugs able to affect epileptogenesis and/or the study of related neuropsychiatric comorbidities. No systematic study has investigated the effects of chronic treatment with antipsychotics or an...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.13121
更新日期:2015-06-01 00:00:00
abstract::1. The effect on systemic haemodynamics of BQ-123, a selective endothelin A (ETA) receptor antagonist, was investigated in healthy men by giving, on separate occasions, ascending intravenous doses of 100, 300, 1000 and 3000 nmol min(-1) BQ-123, each for 15 min, in a randomized, placebo-controlled, double-blind study. ...
journal_title:British journal of pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1038/sj.bjp.0704304
更新日期:2001-10-01 00:00:00
abstract::1. The possible roles of endothelial and smooth muscle cell hyperpolarization and nitric oxide (NO) in endothelium-dependent relaxation were examined in isolated rings of pig right coronary artery. 2. The effects of hyperpolarization were prevented with high K+ (30-125 mM), isotonic Krebs solutions. Functional antagon...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1994.tb13110.x
更新日期:1994-06-01 00:00:00
abstract::In intact mesenteric arteries, increasing [K(+)]o by 5 mM hyperpolarized both endothelial and smooth muscle cells. Subsequent exposure to 10 microM phenylephrine depolarized both cell types which were then repolarized by a 5 mM increase in [K(+)]o. In endothelium-denuded vessels, increasing [K(+)]o by 5 mM hyperpolari...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704256
更新日期:2001-09-01 00:00:00
abstract::1. The modulation of L-type calcium channel current (ICa) by fendiline, a diphenylalkylamine type of calcium channel blocker was investigated on guinea-pig ventricular myocytes by use of the whole-cell patch-clamp technique. 2. Fendiline-induced block of ICa is accompanied by modulation of the channel kinetics in a co...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1992.tb14308.x
更新日期:1992-05-01 00:00:00
abstract::An increasing number of examples in the literature suggest that the in vivo duration of drug action not only depends on macroscopic pharmacokinetic properties like plasma half-life and the time needed to equilibrate between the plasma and the effect compartments, but is also influenced by long-lasting target binding a...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1476-5381.2010.00936.x
更新日期:2010-10-01 00:00:00
abstract::The role of cyclo-oxygenase-1 (COX-1) and cyclo-oxygenase-2 (COX-2) in the upper urinary tract of the guinea-pig and rat was examined using simultaneous tension recordings of the proximal and distal regions of the renal pelvis and the ureter. The guinea-pig upper urinary tract contracted at a frequency (7.52+/-0.3 min...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703104
更新日期:2000-02-01 00:00:00
abstract::1. In order to investigate the vasodilator mechanisms of the K+ channel openers, cromakalim, pinacidil and nicorandil, we measured changes in cytoplasmic Ca2+ concentration [( Ca2+]i) simultaneously with force by a microfluorimetric method using fura-2, a calcium indicator, in canine coronary arterial smooth muscle ce...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1990.tb12106.x
更新日期:1990-09-01 00:00:00
abstract::The effects of adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), and adenosine on compound action potentials were investigated in de-sheathed frog-sciatic nerve preparations. ATP and ADP but not adenosine antagonized the inhibitory action of tetrodotoxin (TTX) on nerve conductio...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1984.tb10075.x
更新日期:1984-02-01 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::1. In the rat isolated diaphragm preparation hexamethonium and other low potency competitive antagonists of acetylcholine (ACh), including gallamine and hyoscine butylbromide, reverse block by the potent antagonists tubocurarine, pancuronium and alcuronium. 2. In the presence of tubocurarine, hexamethonium increases t...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1975.tb07414.x
更新日期:1975-05-01 00:00:00