Abstract：
:Neuropeptide Y (NPY), one of the most abundant peptides in rat and human brains, appears to act in the hypothalamus to stimulate feeding. It was first suggested that the NPY Y1 receptor (Y1R) was involved in feeding stimulated by NPY. More recently a novel NPY receptor subtype (Y5R) was identified in rat and human as the NPY feeding receptor subtype. There is, however, no absolute consensus since selective Y1R antagonists also antagonize NPY-induced hyperphagia. Nevertheless, new anti-obesity drugs may emerge from further pharmacological characterization of the NPY receptors and their antagonists. A large panel of Y1R and Y5R antagonists (such as CGP71683A, BIBO3304, BIBP3226, 1229U91, and SYNAPTIC and BANYU derivatives but also patentable in-house-synthesized compounds) have been evaluated through in vitro and in vivo tests in an attempt to establish a predictive relationship between the binding selectivity for human receptors, the potency in isolated organs assays, and the inhibitory effect on food intake in both normal and obese hyperphagic rodents. Although these results do not allow one to conclude on the implication of a single receptor subtype at the molecular level, this approach is crucial for the design of novel NPY receptor antagonists with potential use as anti-obesity drugs and for evaluation of their possible adverse peripheral side effects, such as hypotension.
journal_name
Can J Physiol Pharmacoljournal_title
Canadian journal of physiology and pharmacologyauthors
Duhault J,Boulanger M,Chamorro S,Boutin JA,Della Zuana O,Douillet E,Fauchère JL,Félétou M,Germain M,Husson B,Vega AM,Renard P,Tisserand Fsubject
Has Abstractpub_date
2000-02-01 00:00:00pages
173-85issue
2eissn
0008-4212issn
1205-7541journal_volume
78pub_type
杂志文章abstract：:Rhus tripartitum D.C., Anacardiaceae, has traditionally been used in Tunisia against many illnesses. The present study investigates, for the first time, the protective effects of the methanol extract of Rhus tripartitum fruit (MERT) against CCl4-induced hepatotoxicity and cisplatin-induced nephrotoxicty in Wistar rats...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/cjpp-2016-0029
更新日期：2016-08-01 00:00:00
abstract：:Recent lines of evidence suggest that the beneficial effects of olive oil are not only related to its high content of oleic acid, but also to the antioxidant potential of its polyphenols. The aim of this work was determine the effects of olive oil and its components, oleic acid and the polyphenol dihydroxyphenylethano...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y05-124
更新日期：2006-02-01 00:00:00
abstract：:The measurement of the sodium reversal potential (Erev), as that potential where the early current reverses during voltage clamp, was found to exceed the true Erev by 4.1 +/- 2.4 mV (mean +/- SD) in squid giant axon. This error was found in both intact and internally perfused axons and is due to interference from the ...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y82-227
更新日期：1982-12-01 00:00:00
abstract：:We found when L-type calcium current (ICa-L) was recorded with the perforated patch-clamp method in rat ventricular myocytes that bath application of phenylephrine (with propranolol) evoked a biphasic response characterized by an initial transient suppression followed by a sustained potentiation. The transient suppres...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y05-058
更新日期：2005-11-01 00:00:00
abstract：:Longitudinal muscle of myometrial tissues from immature rats were examined by quantitative thin section electron microscopy for the presence of gap junctions after treatment with estradiol with and without tamoxifen, and cycloheximide for 1-6 days. Gap junctions were present between myometrial cells on days 4, 5, and ...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y86-117
更新日期：1986-06-01 00:00:00
abstract：:Negative chronotropic effects of beta-adrenoceptor (betaAR) antagonists on right atria from reserpine-treated rats and mice were determined as a test of their inverse agonist activities. BetaAR antagonist ICI-118,551 and nonselective betaAR antagonists alprenolol, propranolol, and timolol produced negative chronotropi...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：
更新日期：1999-12-01 00:00:00
abstract：:The effects of neurokinins (NK) and related peptides on the secretion of 6-keto-prostaglandin F1 alpha, a stable metabolite of prostacyclin, were measured. These peptides enhanced three- to five-fold the basal secretion rate with the following rank order of potency (based on threshold concentrations for a significant ...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y89-026
更新日期：1989-02-01 00:00:00
abstract：:Physical activity and training have some potential as tools for examining immune responses to inflammation and trauma. Contributors to the present symposium review various aspects of the inflammatory process, including issues of lymphocyte recirculation and endotoxemia. They examine also the extent and nature of the i...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章,评审
doi：10.1139/cjpp-76-5-469
更新日期：1998-05-01 00:00:00
abstract：:The endothelium, although only a single layer of cells lining the vascular and lymphatic systems, contributes in multiple ways to vascular homeostasis. Subsequent to the 1980 report by Robert Furchgott and John Zawadzki, there has been a phenomenal increase in our knowledge concerning the signalling molecules and path...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章,评审
doi：10.1139/y2012-073
更新日期：2012-06-01 00:00:00
abstract：:It is possible to embed the control and computation of a simple single-joint movement at different speeds by a small non-linear network of neuron-like elements. The network "learns" by appropriate adjustment of the strengths of interconnection, or synaptic weights, between the neuron-like elements. The learning of a f...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y90-019
更新日期：1990-01-01 00:00:00
abstract：:NTPDase is one of the principal enzymes involved in the sequential hydrolysis of ATP. In the present study, the presence and functionality of NTPDase in the mesenteric vein and artery were examined. Adenosine triphosphate (ATP) (0.01-1000 pmol) induces a dose-dependent vasodilation in the isolated arterial and venous ...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y03-043
更新日期：2003-03-01 00:00:00
abstract：:The purposes of this review were twofold: to apply modern physicochemical principles to explain changes in acid-base regulation and the control of ventilation in human pregnancy; and to demonstrate the value of pregnancy as a model for the study of endocrine effects on physiological control systems. Application of P.A...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章,评审
doi：10.1139/cjpp-76-9-815
更新日期：1998-09-01 00:00:00
abstract：:A variety of porphyrinogenic xenobiotics cause mechanism-based inactivation of a number of rat hepatic cytochrome P450 isozymes. As a result, a mixture of four N-alkylprotoporphyin IX (N-alkylPP) regioisomers, with ferrochelatase-inhibitory properties, are formed. This study was designed to determine whether all four ...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：
更新日期：1996-08-01 00:00:00
abstract：:The development of the febrile response to E. coli lipopolysaccharide (1.5 micrograms/kg, i.v.) in thyroid-deficient rabbits has been studied. Twenty-eight New Zealand White rabbits weighing 2.1-2.3 kg were used. Hypothyroidism was induced by treatment with propylthiouracil (100 or 200 mg/kg body wt./15 days). Thyroid...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y87-209
更新日期：1987-06-01 00:00:00
abstract：:The effect of intracerebroventricular (i.c.v.) injection of the alpha 2-adrenoceptor agonists clonidine and B-HT 920 on mean arterial pressure (MAP), heart rate (HR), and plasma concentrations of noradrenaline and adrenaline was examined in conscious unrestrained rats. The injection of 1.0 microgram clonidine signific...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y88-237
更新日期：1988-11-01 00:00:00
abstract：:We have investigated the influence of dopaminergic agents on the expression of brain-derived neurotrophic factor (BDNF) gene in relation with lipid levels in chronic mild stress (CMS). Mice subjected to CMS were treated with simvastatin (10 mg/kg, per os (orally)) along with bromocriptine (2 mg/kg, intraperitoneally (...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/cjpp-2014-0125
更新日期：2014-12-01 00:00:00
abstract：:Immediately following exposure to thiocyanate (SCN-)-containing solutions, the cystic fibrosis conductance regulator Cl- channel exhibits high unitary SCN conductance and anomalous mole fraction behaviour, suggesting the presence of multiple anion binding sites within the channel pore. However, under steady-state cond...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：
更新日期：2001-07-01 00:00:00
abstract：:The effect of hemorrhagic shock, hypoxemia, and anoxia on the levels of adenine and pyridine nucleotides of liver and kidney was assessed. ATP levels in liver and kidney of animals in shock or animals subjected to 7 min of anoxia decreased by 85 and 73%, respectively. Under hypoxic conditions (arterial PO2 AT 18 MMHg)...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y76-104
更新日期：1976-10-01 00:00:00
abstract：:The effects of estrogen and progesterone domination, achieved by administering estrogen (E) and estrogen plus progesterone (E + P), on rat uterine reactivity to Ca2+ and to Ca2+ channel ligands (antagonist and activator) were compared. The inhibitory activities of nifedipine, diltiazem, and D 600 against K+ depolariza...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y87-327
更新日期：1987-10-01 00:00:00
abstract：:17 beta-Hydroxy-11 beta(4-dimethylaminophenyl)-17 alpha-(1-propynyl)estra-4, 9-dien-3-one (RU486) inhibited the in vitro development of different stages of mouse preimplantation embryos under study. Two-celled embryos, morulae, and early blastocysts were obtained from B6D2F1 mice. The embryos were grown in Ham F-10 nu...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y90-220
更新日期：1990-11-01 00:00:00
abstract：:The contractile recoverability of isolated portal veins made hypodynamic by removal of glucose from the perfusion medium by diverse exogenous substrates was studied. It was found that glucose, mannose, pyruvate, lactate, acetate, and butyrate readily restored contraction. The effects of anoxia and metabolic inhibitors...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y80-115
更新日期：1980-06-01 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：: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：:This study evaluated the in vitro expression of bone-related proteins by osteoblasts in the presence of different concentrations of human recombinant bone morphogenetic protein-2 (rhBMP-2). Immortalized human fetal osteoblastic cell line 1.19 (hFOB) were exposed to different concentrations of rhBMP-2 (10, 50, or 100 n...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/cjpp-2013-0080
更新日期：2013-11-01 00:00:00
abstract：:Our studies are guided by the novel hypothesis that protein tyrosine phosphorylation is an important mechanism for regulating contraction of smooth muscle. Several lines of evidence are reviewed which suggest that enhanced tyrosine phosphorylation participates in mechanisms that regulate cytosolic Ca2+ and Ca2+ sensit...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章,评审
doi：10.1139/y94-207
更新日期：1994-11-01 00:00:00
abstract：:The world-wide increase in cancer incidence imposes a corresponding significant increase in the use of chemotherapeutic agents. Nephrotoxicity is a side effect frequently encountered with cyclophosphamide (CP), which is also well-known to cause acute and chronic lung toxicities. The current study focuses on the evalua...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/cjpp-2015-0070
更新日期：2016-04-01 00:00:00
abstract：:The isometric contractile properties of frog (Rana pipiens) and toad (Bufo bufo) sartorii have been studied over the temperature range from 0 to 20 degrees C. The isometric twitch tension was found to vary considerably between these two species and between muscles in the same species. Between 0 and 4 degrees C there w...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y81-082
更新日期：1981-06-01 00:00:00
abstract：:Using radioligand binding techniques, the effect of reserpine pretreatment on ventricular adrenergic receptors from guinea pig was studied. [3H]Prazosin and [3H]dihydroalprenolol were used to label alpha 1- and beta-adrenergic receptors, respectively. Administration of 2.5 mg/kg reserpine for 2 days caused a significa...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y84-003
更新日期：1984-01-01 00:00:00
abstract：:The effects of fast neutrons (10-100 Gy) on chromatin extracted from normal (liver of Wistar rats) and tumor (Walker carcinosarcoma maintained on Wistar rats) tissues were compared. The spectroscopic assays used were (i) chromatin intrinsic fluorescence, (ii) time-resolved fluorescence of chromatin - proflavine comple...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y02-087
更新日期：2002-07-01 00:00:00
abstract：:Effects of xanthine--xanthine oxidase produced oxygen radicals were studied in hypertrophied rat hearts in a Langendorff preparation. Heart hypertrophy was produced by banding of the abdominal aorta for 6 weeks. This resulted in a 22% increase in ventricle/body weight ratio compared with that of sham-operated controls...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y87-183
更新日期：1987-06-01 00:00:00
