Abstract：
:The 3,5-pyrazolidinedione (3,5-P) drugs, phenylbutazone and sulfinpyrazone, have been reported to bind to receptors for the chemotactic peptide, f-Met-Leu-Phe, and to behave as functional antagonists of f-Met-Leu-Phe in human and rabbit neutrophils. To explore the structure-activity relationship of this family of drugs for f-Met-Leu-Phe receptor binding, 36 drugs with the 3,5-P structure, a structure related to antipyrine, or an unrelated structure were tested as competitors for the binding of f-Met-Leu-Phe-Lys-fluorescein isothiocyanate on human neutrophils by flow cytometric analysis. Only drugs possessing the 3,5-P ring were significant competitors. The five most potent 3,5-Ps behaved as selective antagonists of f-Met-Leu-Phe-induced superoxide anion release by neutrophils. The potency was not correlated to the pKa or to their capacity to inhibit prostaglandin E2 released from culture fibroblasts but instead appeared to be correlated to their apparent octanol-buffer partition coefficients. The most potent f-Met-Leu-Phe antagonist identified, 1,2-diphenyl-4-(3-(1-naphthyl)-propyl)-3,5-pyrazolidinedione (DPN), may also possess an improved pharmacodynamic specificity compared with phenylbutazone and sulfinpyrazone, as it was less potent than phenylbutazone in the inhibition of prostaglandin synthesis and it was not cytotoxic. DPN may be a prototype for a valuable new class of anti-inflammatory drugs.
journal_name
Can J Physiol Pharmacoljournal_title
Canadian journal of physiology and pharmacologyauthors
Levesque L,Gaudreault RC,Marceau Fdoi
10.1139/y91-064subject
Has Abstractpub_date
1991-03-01 00:00:00pages
419-25issue
3eissn
0008-4212issn
1205-7541journal_volume
69pub_type
杂志文章abstract：:The effects of the dopamine type-2 receptor (D-2) antagonist domperidone on pituitary and brain amine concentrations and serum gonadotropin levels in the goldfish were investigated. Domperidone caused a long-lasting, dose-dependent depletion of dopamine in the goldfish pituitary. Pituitary concentrations of 5-hydroxyt...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y91-116
更新日期：1991-06-01 00:00:00
abstract：:The calyx-type synapse of the embryonic chick ciliary ganglion is reviewed as a model of transmitter release from a vertebrate presynaptic nerve terminal. This nerve terminal is extensive in area, enabling the penetration with microelectrodes and the application of patch-clamp techniques. In other respects the calyx s...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章,评审
doi：10.1139/y92-246
更新日期：1992-01-01 00:00:00
abstract：:Our objective was to determine the effects of a clenbuterol (CB) treatment orally administered (2 mg per kg) to rats submitted to 14 days of hindlimb unloading (HU). The morphological and the contractile properties as well as the myosin heavy chain isoforms contained in each fiber type were determined in whole soleus ...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y04-034
更新日期：2004-05-01 00:00:00
abstract：:Neonatal hyperthyroidism (NH) in the rat is associated with permanent reductions in serum thyroxine (T4), triiodothyronine (T3), and thyroid-stimulating hormone (TSH) concentrations in the adult, changes suggestive of a hypothyroid state. In the adult NH rat, the thyrotroph appears to be more sensitive to the feedback...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y85-188
更新日期：1985-09-01 00:00:00
abstract：:Cold ischemia--warm reperfusion (CI/WR) injury of liver transplantation involves hepatocyte cell death, the nature and underlying mechanisms of which remain unclear. Isolated hepatocytes and isolated perfused livers were used to determine the prevalence of necrosis and apoptosis as well as mitochondrial dysfunction. I...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y06-014
更新日期：2006-05-01 00:00:00
abstract：:Liver blood flow and hepatic uptake of some indicator substances have been reported to fall with age in both rats and humans. We used an isolated liver system, which was perfused in one pass with hemoglobin free buffer, to investigate the effect of albumin concentration, buffer flow rate, and age upon hepatic clearanc...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y88-091
更新日期：1988-05-01 00:00:00
abstract：:The influence of a program of high intensity training and of a combined program of high intensity training and prolonged submaximal training on adaptations to the vastus lateralis muscle was investigated in two groups of elite athletes. The high intensity training (H) consisted of ice hockey practices and games over a...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y82-085
更新日期：1982-05-01 00:00:00
abstract：:Two principles suffice to model the large-scale geometry of normal human coronary arterial networks. The first principle states that artery diameters are set to minimize the power required to distribute blood through the network. The second principle states that arterial tree geometries are set to globally minimize th...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：
更新日期：2000-08-01 00:00:00
abstract：:The effects of clofibrate administration (200 mg/kg, po) on somatic growth, plasma levels of lipids, tryptophan, growth hormone (GH), and prolactin (PRL), as well as on brain concentrations of tryptophan and 5-hydroxytryptamine (5-HT) were studied in prepubertal male rats. The drug did not significantly alter ponderal...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y78-039
更新日期：1978-04-01 00:00:00
abstract：:Hepatotoxicity and nephrotoxicity are important drawbacks of cisplatin. The objective of this study is to evaluate the ability of ambroxol in 2 different doses (35 and 70 mg/kg, i.p.) to protect liver and kidney from damage induced by a single dose of cisplatin (10 mg/kg, i.p.) in comparison with N-acetylcysteine (250...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/cjpp-2018-0528
更新日期：2019-01-01 00:00:00
abstract：:Studies are scant on the effects of short-term carvedilol treatment as an adjuvant to angiotensin-converting enzyme (ACE) inhibitor in patients with left ventricular (LV) systolic dysfunction. The objective of this study was to find the effects of short-term treatment of carvedilol on patients with ischemic LV systoli...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1139/y07-006
更新日期：2007-02-01 00:00:00
abstract：:When carbon tetrachloride (CCl4) was administered to rats, a localized region of hepatic edema could be detected within 1 h by in vivo proton magnetic resonance imaging. However, if rats were pretreated with gadolinium chloride (GdCl3), an inhibitor of Kupffer cell function, the CCl4-induced edema was greatly decrease...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y94-064
更新日期：1994-05-01 00:00:00
abstract：:In male Sprague--Dawley rats, hypertensive development was diminished for 10 weeks when parathyroidectomy (PTX) was performed 1 week before deoxycorticosterone plus saline (DOCA + NaCl) treatment. In young spontaneously hypertensive male rats (SHR, Okamoto strain) parathyroidectomy performed after weaning lessened hyp...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y82-033
更新日期：1982-02-01 00:00:00
abstract：:Selected parameters of cardiovascular function were evaluated in vitamin A-deficient rats at 70 days of age. Resting heart rate was increased by an average of 100 bpm (21.4+/-2.7%), whereas resting systolic blood pressure was normal in vitamin A-deficient animals. The maximal contractile force developed per milligram ...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y01-093
更新日期：2002-01-01 00:00:00
abstract：:Uroporphyrinogen decarboxylase (UROG-D) activity in the 10,000g supernatant of 17-day-old chick embryo liver homogenates was determined by measuring the conversion of pentacarboxylporphyrinogen I to coproporphyrinogen I. The optimum pH of the enzyme was found to be approximately 6.0 and enzyme activity was found to be...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y89-041
更新日期：1989-03-01 00:00:00
abstract：:A survey of 'steady-state' serum levels of anticonvulsant drugs from 221 epileptic patients at a university hospital was conducted. Serum concentrations of phenobarbital, primidone, and diphenylhydantoin were determined by a gas chromatographic method. Sixty-five percent (130) of the patients receiving diphenylhydanto...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y76-119
更新日期：1976-12-01 00:00:00
abstract：:Molecular mechanisms by which exercise exerts cardiovascular benefits are poorly understood. Exercise-induced increase of endothelial NO synthase (eNOS) phosphorylation through the protein kinase Akt has been shown to be a key mechanism underlying the beneficial effect of exercise in coronary artery disease patients. ...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y10-107
更新日期：2011-01-01 00:00:00
abstract：:Geraniol, a plant-derived monoterpene, has been extensively studied and showed a wide variety of beneficial effects. The aim of this study was to investigate the therapeutic effect of geraniol on functional recovery and neuropathic pain in rats with spinal cord injury (SCI). Rats received a clip-compression SCI and we...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/cjpp-2016-0528
更新日期：2017-12-01 00:00:00
abstract：:The reported efficiencies of drug encapsulation into liposomes range from less than 0.1% to more than 10% per micromole phospholipid, depending on the nature of the drug and of the liposome employed. We have sought to investigate some of the factors which control the efficiency of drug encapsulation. We have found tha...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y79-081
更新日期：1979-05-01 00:00:00
abstract：:We have measured the responses to endurance exercise training on body composition and glucose regulation, as well as cardiovascular and liver structure and function in rats fed a high carbohydrate and high fat (HCHF) diet as a model of human metabolic syndrome. Male Wistar rats (9-10 weeks old) were randomly allocated...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y2012-097
更新日期：2012-11-01 00:00:00
abstract：:Oxidative stress plays a vital role in the pathogenesis of neurodegenerative diseases. Chikusetsu saponin V (CsV), the most abundant member of saponins from Panax japonicus (SPJ), has attracted increasing attention for its potential to treat neurodegenerative diseases. However, the mechanisms are unclear. Our study in...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/cjpp-2015-0262
更新日期：2016-09-01 00:00:00
abstract：:As an activator of AMPK, the effect of AICAR on insulin signaling has not been investigated extensively. PI3K-Akt is a critical node involved in the insulin signaling pathway. We observed that concomitant with the activation of AMPK by AICAR, the protein level of PI3K p85α and the insulin-induced phosphorylation of Ak...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/cjpp-2015-0159
更新日期：2016-02-01 00:00:00
abstract：:The experiment examined biological responses produced by combined sequential exposure to low-level tritium contamination, followed by challenging irradiation with fast neutrons. Modifications of endogenous antioxidant potential of different organs in rats were discussed in relation to tissue radiosensitivity. Rats pre...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y02-089
更新日期：2002-07-01 00:00:00
abstract：:Single crab (Callinectes danae) fibers were equilibrated with isotonic, high KCl solutions and were subsequently returned to the control saline. This caused marked swelling of the T tubules. Fibers treated with 100 mM KCl had a 2.5-mV residual depolarization, a 50% decrease in effective membrane resistance (Reff) and ...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y85-144
更新日期：1985-07-01 00:00:00
abstract：:We investigated the effects of 4% fructose plus moderately high salt (MHS) (4% NaCl) treatment on tissue aldehyde conjugates, platelet cytosolic free calcium ([Ca2+]i), renal morphology, and systolic blood pressure (SBP) in Wistar-Kyoto rats, and whether these effects were reversible (R) after withdrawal of treatment....
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y06-080
更新日期：2007-03-01 00:00:00
abstract：:The Na+/H+ exchanger isoform 1 is an integral membrane protein that regulates intracellular pH. It extrudes 1 intracellular H+ in exchange for 1 extracellular Na+. It has 2 large domains, an N-terminal membrane domain of 12 transmembrane segments and an intracellular C-terminal regulatory domain. We characterized the ...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y06-081
更新日期：2007-03-01 00:00:00
abstract：:2,4-Dinitrophenol, pentobarbital, thiopental, methoxyflurane, and halothane more often antagonized the facilitatory effects of substance P than of acetylcholine on the activity of spinal dorsal horn neurons (of unanesthetized decerebrated and spinalized cats) as well as interpeduncular and cerebral cortical cells (of ...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y78-082
更新日期：1978-06-01 00:00:00
abstract：:In the wake of demographic change in Western countries, atrial fibrillation has reached an epidemiological scale, yet current strategies for drug treatment of the arrhythmia lack sufficient efficacy and safety. In search of novel medications, atrial-selective drugs that specifically target atrial over other cardiac fu...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章,评审
doi：10.1139/cjpp-2017-0024
更新日期：2017-11-01 00:00:00
abstract：:A brief summary is given of some of the key points of the individual contributions at this International Brain Research Organization satellite meeting, presenting up-to-date, expert knowledge of energy metabolism, ionic turnover, and cell swelling at the cellular level of the mammalian central nervous system. On the b...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章,评审
doi：10.1139/y92-250
更新日期：1992-01-01 00:00:00
abstract：:In addition to cytostatic treatment and surgery, the most common cancer treatment is gamma radiation. Despite sophisticated radiological techniques however, in addition to irradiation of the tumor, irradiation of the surrounding healthy tissue also takes place, which results in various side-effects, depending on the a...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章,评审
doi：10.1139/cjpp-2015-0006
更新日期：2015-09-01 00:00:00
