Abstract:
:In this study we have determined the different signalling pathways involved in adenosine A(1)-receptor (A(1)-receptor)-dependent inhibition of contractility in rat isolated atria. N-cyclopentyladenosine (CPA) stimulation of A(1)-receptor exerts: negative inotropic response, inositol phosphates accumulation, stimulation of nitric oxide synthase (NOS), increased production of nitric oxide (NO) and cyclic GMP. Inhibitors of phospholipase C (PLC), protein kinase C (PKC), calcium/calmodulin, NOS and guanylate cyclase shifted the dose-response curve of CPA on contractility to the right. Those inhibitors also attenuated the A(1)-receptor-dependent increase in cyclic GMP and activation of NOS. These results suggest that CPA activation of A(1)-receptors exerts a negative inotropic effect associated with increased production of nitric oxide and cyclic GMP. The mechanism appears to occur secondarily to stimulation of phosphoinositide turnover via PLC activation. This, in turn, triggers cascade reactions involving calcium/calmodulin and PKC, leading to activation of NOS and soluble guanylate cyclase.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Sterin-Borda L,Gómez RM,Borda Edoi
10.1038/sj.bjp.0704487subject
Has Abstractpub_date
2002-01-01 00:00:00pages
444-50issue
2eissn
0007-1188issn
1476-5381journal_volume
135pub_type
杂志文章abstract::1. DL-1-(2-acetyl-4-n-butyramidophenoxy)-2-hydroxy-3-isopropylaminopropane hydrochloride (M & B 17803A) was given to four healthy volunteers in single oral doses of up to 300 mg. There were no subjective effects and no significant alterations in the heart rate, systolic and diastolic blood pressure in the seated posit...
journal_title:British journal of pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1476-5381.1971.tb07193.x
更新日期:1971-11-01 00:00:00
abstract::1. The irritant fungal terpenoid isovelleral caused protective eye-wiping movements in the rat upon intraocular instillation and showed cross-tachyphylaxis with capsaicin, the pungent principle in hot pepper. 2. Isovelleral induced a dose-dependent calcium uptake by rat dorsal root ganglion neurones cultured in vitro ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb15983.x
更新日期:1996-09-01 00:00:00
abstract::1. The ability of a range of substituted imidazole compounds to inhibit mouse cerebellar neuronal nitric oxide synthase (nNOS), bovine aortic endothelial NOS (eNOS) and inducible NOS (iNOS) from lungs of endotoxin-pretreated rats was investigated. In each case the substrate (L-arginine) concentration employed was 120 ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb16003.x
更新日期:1996-09-01 00:00:00
abstract::1. The effects of the metabotropic glutamate receptor (mGluR) antagonist, L-2-amino-3-phosphonopropionate (L-AP3) on phosphoinositide turnover in neonatal rat cerebral cortex slices has been investigated. 2. At concentrations of < or = 300 microM, L-AP3 inhibited total [3H]-inositol phosphate ([3H]-InsPx) and Ins(1,4,...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb16730.x
更新日期:1996-03-01 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:Sildenafil is a selective inhibitor of cGMP-specific phosphodiesterase. Sildenafil, acting via NO-dependent mechanisms, prevents indomethacin-induced gastropathy. Activation of ATP-sensitive potassium channels (K(ATP)) is involved in gastric defence. Our objective was to evaluate the role of the ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0707605
更新日期:2008-02-01 00:00:00
abstract::1. The aims of the present study were to determine whether long-term 5-hydroxytryptamine (5-HT) reuptake blockade and inhibition of type-A monoamine oxidase (MAO-A) lead to an enhancement of the electrically evoked release of tritum from guinea-pig brain slices preloaded with [3H]-5-HT, and to assess the sensitivity o...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1994.tb17015.x
更新日期:1994-10-01 00:00:00
abstract::1. Anaesthetized, open-chest dogs were subjected to 60 min of left circumflex coronary artery occlusion followed by 90 min of reperfusion. Endothelium-dependent and -independent relaxant responses of the isolated coronary arterial rings were then investigated. 2. The endothelium-dependent, acetylcholine-induced relaxa...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1992.tb09018.x
更新日期:1992-03-01 00:00:00
abstract::1. Intrasplenic injection of bradykinin (BK) induced a dose-dependent pressor response in the anaesthetized cat, with an ED50 of 0.98 +/- 0.43 nmol. In contrast, intrasplenic administration of desArg9bradykinin (desArg9BK) was without significant effect at doses of up to 200 nmol. 2. Intravenously administered BK indu...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1993.tb13962.x
更新日期:1993-12-01 00:00:00
abstract::1 We have examined the effect of the histone deacetylase inhibitors apicidin, trichostatin A (TSA) and n-butyrate on the histone acetylation and the differentiation of human eosinophilic leukemia HL-60 clone 15 cells into eosinophils. 2 Viability of the cells incubated with apicidin (100 nm), TSA (30 nm) or n-butyrate...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705869
更新日期:2004-07-01 00:00:00
abstract::Pulmonary fibrosis represents the end stage of a number of heterogeneous conditions and is, to a greater or lesser degree, the hallmark of the interstitial lung diseases. It is characterized by the excessive deposition of extracellular matrix proteins within the pulmonary interstitium leading to the obliteration of fu...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1476-5381.2011.01247.x
更新日期:2011-05-01 00:00:00
abstract::1. The vasodilator responses of isolated intrapulmonary arteries (IPA) to P2-receptor agonists were investigated during adaptation to extrauterine life in the piglet. The effect of pulmonary hypertension on the normal response was determined after exposing newborn animals to chronic hypobaric hypoxia (51 kPa) for 3 da...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702815
更新日期:1999-10-01 00:00:00
abstract::1. The neurotransmitters involved in NANC relaxation and their possible interactions were investigated in mouse isolated stomach, recording the motor responses as changes of endoluminal pressure from whole organ. 2. Field stimulation produced tetrodotoxin-sensitive, frequency-dependent, biphasic responses: rapid trans...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705431
更新日期:2003-09-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Pelitinib is a potent irreversible EGFR TK inhibitor currently in clinical trials for the treatment of lung cancer. Hyperthermia has been applied concomitantly with chemotherapy and radiotherapy to enhance treatment outcome. In this study, we investigated the ability of the combination of pelitin...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.13189
更新日期:2015-08-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Pituitary adenylate cyclase-activating polypeptide (PACAP) is an excitatory neuropeptide with central and peripheral cardiovascular actions. Intrathecal PACAP increases splanchnic sympathetic nerve activity and heart rate, but not mean arterial pressure (MAP). We hypothesize that the three PACAP ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2012.02045.x
更新日期:2012-11-01 00:00:00
abstract::1. The central and regional cardiovascular responses to intravenous (0.3, 1.0, 3.0 and 10.0 micrograms kg-1 min-1) and intracoronary (0.3, 0.9, 3.0 and 4.5 micrograms kg-1 min-1) infusions of elgodipine, a phenyldihydropyridine, and its solvent were studied in anaesthetized pigs. 2. Elgodipine (i.v.) caused dose-depen...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1990.tb14708.x
更新日期:1990-02-01 00:00:00
abstract::1. Changes induced in the electrocorticogram by the bilateral perfusion of (+)-amphetamine into the mesencephalic reticular formation (MRF) have been studied in cat encéphale isolé preparations. 2. (+)-Amphetamine, applied for 5 min in the MRF, mimicked the electrocortical desynchronization induced by the perfusion of...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1977.tb08424.x
更新日期:1977-11-01 00:00:00
abstract::1. The effect of [Na]o on the catecholamine release evoked by K in ouabain pretreated, isolated adrenal glands of the cat, was investigated. 2. Reduction of [Na]o to 70, 50 and 25 mM, with sucrose as a substitute, did not modify the spontaneous catecholamine release but progressively increased the K (17.7 mM)-evoked s...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1989.tb12618.x
更新日期:1989-10-01 00:00:00
abstract:BACKGROUND AND PURPOSE:While selective, bitter tasting, TAS2R agonists can relax agonist-contracted airway smooth muscle (ASM), their mechanism of action is unclear. However, ASM contraction is regulated by Ca²⁺ signalling and Ca²⁺ sensitivity. We have therefore investigated how the TAS2R10 agonists chloroquine, quinin...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.12460
更新日期:2014-02-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Gain of function mutations in TRPC6 channels can cause autosomal dominant forms of focal segmental glomerulosclerosis (FSGS). Validated inhibitors of TRPC6 channels that are biologically active on FSGS-related TRPC6 mutants are eagerly sought. EXPERIMENTAL APPROACH:We synthesized new TRPC6-inhib...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.13977
更新日期:2017-11-01 00:00:00
abstract::1 To evaluate the role of prostaglandin I(2) (PGI(2)) in allergic inflammation, allergic responses in the airway, skin and T cells were studied in mice lacking the receptor for PGI(2) (the prostanoid IP receptor) through gene disruption. 2 Three inhalations of antigen caused an increase in plasma extravasation, leukoc...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704872
更新日期:2002-10-01 00:00:00
abstract::1 The isolated perfused ear of the rabbit connected to the body only by its nerve, was used to investigate the influence of prostaglandin F2alpha on the algesic effect of bradykinin and acetylcholine. 2 Bradykinin and acetylcholine, following intra-arterial injection into the isolated perfused ear elicited a dose-rela...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1977.tb08390.x
更新日期:1977-03-01 00:00:00
abstract::1. U937 cells are a continuous line of human cells of committed monocytic origin which serve as a useful model for studying human monocytic function. The present study investigated the effect of platelet-activating factor (Paf) on intracellular free calcium ion concentration ([Ca2+]i) in U937 cells using the calcium f...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1988.tb11461.x
更新日期:1988-04-01 00:00:00
abstract::Robert F. Furchgott, pharmacologist and joint winner of the Nobel Prize for Medicine or Physiology (1998) died on the 12th of May 2009 aged 92. By unlocking the astonishingly diverse biological actions of nitric oxide, Furchgott leaves behind a rich legacy that has both revolutionized our understanding of human physio...
journal_title:British journal of pharmacology
pub_type: 传,社论,历史文章
doi:10.1111/j.1476-5381.2009.00418.x
更新日期:2009-10-01 00:00:00
abstract::S-nitrosothiols have a number of potential clinical applications, among which their use as antithrombotic agents has been emphasized. This is largely because of their well-documented platelet inhibitory effects, which show a degree of platelet selectivity, although the mechanism of this remains undefined. Recent progr...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1476-5381.2010.00670.x
更新日期:2010-04-01 00:00:00
abstract::1. Regulation of the increase in inositol-1,4,5-trisphosphate (IP3) production and intracellular Ca2+ concentration ([Ca2+]i by protein kinase C (PKC) was investigated in canine cultured tracheal smooth muscle cells (TSMCs). Stimulation of TSMCs by 5-hydroxytryptamine (5-HT) caused an initial transient [Ca2+]i peak fo...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701195
更新日期:1997-07-01 00:00:00
abstract::1. Phenylephrine-induced contractions of rabbit isolated trigone and urethra were antagonized in a competitive manner by alfuzosin (pA2 7.44 and 7.30, respectively) and prazosin. 2. The characteristics of [3H]-prazosin binding to human prostatic adenoma tissue were evaluated. [3H]-prazosin was potently displaced by al...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1993.tb13762.x
更新日期:1993-08-01 00:00:00
abstract::1. Membrane effects of cromakalim (Crom; 50-300 microM) were examined in CA1 neurones recorded mainly by intracellular, single-electrode voltage-clamping in slices (from Sprague-Dawley rats) kept in an interface chamber at 33 degrees C. 2. In 14 cells held at -63 +/- 3.5 mV, in the presence of tetrodotoxin, kynurenic ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1994.tb17004.x
更新日期:1994-10-01 00:00:00
abstract::Hydrogen sulfide (H(2)S) is described as a mediator of diverse biological effects, and is known to produce irritation and injury in the lung following inhalation. Recently, H(2)S has been found to cause contraction in the rat urinary bladder via a neurogenic mechanism. Here, we studied whether sodium hydrogen sulfide ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0706277
更新日期:2005-08-01 00:00:00
abstract:BACKGROUND AND PURPOSE:It is well known that adenine-based purines exert multiple effects on pain transmission. However, less attention has been given to the potential effects of guanine-based purines on pain transmission. The aim of this study was to investigate the effects of intraperitoneal (i.p.) and oral (p.o.) ad...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2009.00597.x
更新日期:2010-03-01 00:00:00