Abstract：
:This paper discusses the discovery of ligands for orphan receptors and the identification of the natural endogenous ligands for those receptors in physiology. The central thesis is that orphan seven transmembrane receptors (7TMRs) are allosteric conduits of chemical information exchange from extracellular ligands to intracellar signaling mechanisms. This being the case, the optimal systems for discovery of orphan ligands must be synoptic in nature, that is, include the allosteric co-binding species that interact with the receptor since this latter component is essential for normal orphan 7TMR function. Constitutively active orphan receptor systems are also discussed as useful testing systems for orphan ligands. This is because the activated orphan receptor has a heightened sensitivity to cellular signaling species and thus whole cell constitutively active systems become sensitive to ligand binding. Finally, the phenomenon of biased signaling (due to stabilization of unique receptor active conformations) is discussed as a roadblock to the definitive identification of the natural orphan ligand but not to the detection of ligand tools to elucidate orphan 7TMR function.
journal_name
Pharmacol Resjournal_title
Pharmacological researchauthors
Kenakin TPdoi
10.1016/j.phrs.2016.01.022subject
Has Abstractpub_date
2016-12-01 00:00:00pages
284-290eissn
1043-6618issn
1096-1186pii
S1043-6618(16)00024-4journal_volume
114pub_type
杂志文章,评审abstract：:Respiratory fluoroquinolones are currently considered by several guidelines among the most effective antimicrobial agents for the treatment of acute bacterial rhinosinusitis. The aim of this study was to assess levofloxacin penetration into paranasal sinuses mucosa of 15 patients with chronic rhinosinusitis 1h (n = 4)...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2006.10.003
更新日期：2007-01-01 00:00:00
abstract：:HMG-CoA reductase inhibitors (statins) have been shown to improve cardiovascular (CV) outcomes in the general population as well as in patients with cardiovascular disease (CVD). Statins' beneficial effects have been attributed to both cholesterol-lowering and cholesterol-independent "pleiotropic" properties. By their...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2014.06.011
更新日期：2014-10-01 00:00:00
abstract：:Biochemical evaluations of the effects of the sulfhydryl-containing angiotensin-converting enzyme inhibitor (captopril) on the nephrotoxicity induced by doxorubicin in normal rats were carried out. A single dose of doxorubicin (15 mg kg-1) which caused nephrotoxicity was manifested biochemically by the elevation of se...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1006/phrs.1998.0432
更新日期：1999-03-01 00:00:00
abstract：:The endocannabinoid signalling system includes: (1) at least two G-protein-coupled receptors, known as the cannabinoid CB(1) and CB(2) receptors and discovered following studies on the mechanism of action of Delta(9)-tetrahydrocannabinol, the major psychoactive principle of the hemp plant Cannabis sativa; (2) the endo...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2009.02.010
更新日期：2009-08-01 00:00:00
abstract：:Nerve growth factor (NGF) is the prototype of the neurotrophin family and promotes the survival of specific populations of neurons, stimulates their morphological differentiation and regulates neuronal gene expression. Since its discovery, NGF attracted clinicians for its potential application in the treatment of neur...
journal_title：Pharmacological research
pub_type： 临床试验,杂志文章
doi：10.1016/j.phrs.2007.03.007
更新日期：2007-07-01 00:00:00
abstract：:The apelinergic system is an important player in the regulation of both vascular tone and cardiovascular function, making this physiological system an attractive target for drug development for hypertension, heart failure and ischemic heart disease. Indeed, apelin exerts a positive inotropic effect in humans whilst re...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2018.02.032
更新日期：2018-05-01 00:00:00
abstract：:The uridin-diphosphoglucuronyl-transferase (UDP-GT) is a membrane-bound enzyme responsible for glucuronidation of endogenous and exogenous compounds. This work established the UDP-GT activity and its lipid membrane microenvironment in two experimental models: acute paracetamol intoxication, and cholestasis followed by...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1006/phrs.1999.0530
更新日期：1999-10-01 00:00:00
abstract：:The molecular complexity of human breast cancer (BC) renders the clinical management of the disease challenging. Long non-coding RNAs (lncRNAs) are promising biomarkers for BC patient stratification, early detection, and disease monitoring. Here, we identified the involvement of the long intergenic non-coding RNA 0108...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2020.105249
更新日期：2020-11-01 00:00:00
abstract：:Sesquiterpene lactones (SL) are natural bioactive molecules indicated as potential scaffolds for anti-inflammatory and analgesic drug design. However, their anti-inflammatory applicability remains underestimated since the impact of SL on inflammatory nociception and tissue repair are overlooked. Thus, we used an integ...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2020.105303
更新日期：2020-11-16 00:00:00
abstract：BACKGROUND:Oxidative stress plays an important role in the occurrence of chronic diseases. Zinc supplementation is also known to be an antioxidant agent. While, there is no review on the effects of zinc supplementation on oxidative stress, this study aimed to systematically summarize randomized clinical trials (RCTs) w...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2020.105166
更新日期：2020-11-01 00:00:00
abstract：:Sepsis induced myocardial dysfunction (SIMD) results in high morbidity and mortality. However, the effective therapeutic strategies for SIMD treatment remain limited. Sirt3 is the main mitochondrial Sirtuin member and is a key modulator of mitochondrial metabolism and function. In this study, we aimed to investigate t...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2020.104887
更新日期：2020-09-01 00:00:00
abstract：:In the present study we evaluated the protective activity of pyridoxol L,2-pyrrolidon-5 carboxylate (metadoxine) against CCl4 intoxication in rats, especially in relation to liver fibrosis. After 6 consecutive weeks of CCl4 treatment, the animals developed liver fibrosis and inflammation as revealed by histological an...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/s1043-6618(05)80067-2
更新日期：1992-01-01 00:00:00
abstract：:Iron is an essential element for virtually all organisms. It facilitates cell proliferation and growth but also contributes to major hallmarks of cancer such as tumor initiation, growth, and metastasis. Often, iron handling of tumor cells is disturbed, with altered iron acquisition, efflux, and storage. Targeting pert...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2017.03.018
更新日期：2017-06-01 00:00:00
abstract：:The mechanism for the pathological increase in cell death in various disease states e.g. HIV immunodefficiency or even ageing or Alzheimer's disease, occurs by complex and as yet undefined mechanism(s) related to immunological, virological or biochemical disturbances (i.e. energy depletion, oxidative stress, increased...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/s1043-6618(05)80044-1
更新日期：1995-12-01 00:00:00
abstract：:Cancer cell mutations can be identified by genomic and transcriptomic techniques. However, they are not sufficient to understand the full complexity of cancer heterogeneity. Analyses of proteins expressed in cancers and their modification profiles show how these mutations could be translated at the functional level. P...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2020.105091
更新日期：2020-10-01 00:00:00
abstract：:The EEG and behavioural changes induced by the administration of polyamines (spermine and spermidine) were studied in rabbit. Spermine and spermidine were administered at different doses (200 and 400 micrograms) into the mesencephalic ventricle (i.c.v.) both as a bolus and in constant perfusion (60 min duration). We a...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/1043-6618(90)90754-2
更新日期：1990-07-01 00:00:00
abstract：:Alzheimer's is the neurodegenerative disease affecting the largest number of patients in the world. In spite of the intense research of the last decades, progress about its knowledge and therapy was limited. In particular, various cytotoxic processes remained debated, while the few drugs approved for therapy were of o...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2019.104316
更新日期：2019-08-01 00:00:00
abstract：:Biosimilars started receiving the marketing authorization by European Medicine Agency since 2006. The development of biosimilars follows a well-defined step-wise approach, the so-called comparability exercise, which aims to compare non-clinical (mainly quality features and biological activity) and clinical (efficacy a...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2017.11.002
更新日期：2017-12-01 00:00:00
abstract：:The metabolism of arachidonic acid by cytochrome P450 (CYP) epoxygenases generates epoxyeicosatrienoic acids (EETs) which affect numerous cellular process including Ca(2+) signaling and the activity of Ca(2+)-dependent K(+) channels. The expression of the CYP epoxygenase(s) that generate EETs in endothelial cells is n...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2003.11.016
更新日期：2004-06-01 00:00:00
abstract：:This article summarizes the discovery and the development of endothelial biology with a special focus on the role of endothelium-dependent vasoconstriction. The physician-scientist Paul Michel Vanhoutte contributed many of the initial observations that helped to understand and form the main concepts of modern vascular...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2011.02.013
更新日期：2011-06-01 00:00:00
abstract：BACKGROUND:We examined the influence of diabetes mellitus (DM) on the healing of HCl-induced gastric lesions and the healing promoting effect of IGF-1 on these lesions. METHODS:Experiments were performed on rats injected with streptozotocin (STZ, 70 mg kg(-1), i.p.) 5 weeks prior to the experimental session. Diabetic ...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1006/phrs.1999.0581
更新日期：2000-02-01 00:00:00
abstract：:Long non-coding RNA (lncRNA) is a class of non-coding RNA with ≥200 nucleotides in length which are involved as critical regulators in various cellular processes. LncRNAs contribute to the development and progression of many human diseases. Autophagy is a key catabolic process which helps to maintain the cellular home...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2019.02.010
更新日期：2019-04-01 00:00:00
abstract：:The Ras-Raf-MEK-ERK (Map kinase) cellular pathway is a highly conserved eukaryotic signaling module that transduces extracellular signals from growth factors and cytokines into intracellular regulatory events that are involved in cell growth and proliferation or the contrary pathway of cell differentiation. Dysregulat...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2016.12.009
更新日期：2017-03-01 00:00:00
abstract：:This study investigated the impact of benzodiazepine receptor agonist, midazolam and antagonist, flumazenil, on the rat frontal cortex slices oxygen consumption (QO(2)), in presence and absence of gamma-aminobutyric acid (GABA). QO(2) was polarographically determined, using the biological oxygen monitor. As it was pre...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/s1043-6618(02)00289-x
更新日期：2003-02-01 00:00:00
abstract：:The investigation was aimed at investigating whether the dopaminergic projection arriving at the nucleus septi lateralis (NSL) is involved in the facilitatory effect of vasopressin (AVP) on memory retrieval. The bilateral 6-OHDA lesions to the NSL were made in 20 male Wistar rats before testing the intracerebroventric...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1006/phrs.1997.0280
更新日期：1998-02-01 00:00:00
abstract：:The potential drug-to-drug interaction between darunavir and raltegravir in the setting of HIV infection is a highly debated issue still unresolved. In the present study we have evaluated the pharmacokinetics of darunavir and ritonavir in 53 HIV-1 infected patients with or without concomitant raltegravir administratio...
journal_title：Pharmacological research
pub_type： 临床试验,杂志文章
doi：10.1016/j.phrs.2011.09.006
更新日期：2012-02-01 00:00:00
abstract：:CHF5074 is a non-steroidal anti-inflammatory derivative holding disease-modifying potential for the treatment of Alzheimer's disease. The aim of the present study was to characterize the electrophysiological and metabolic profile of CHF5074 in the hippocampus. Electrophysiological recordings show that CHF5074 inhibits...
journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2014.02.010
更新日期：2014-03-01 00:00:00
abstract：:Epidemiological studies support an inverse correlation between HDL-C and cardiovascular disease. However, low HDL-C levels do not always segregate with premature disease. These include, LCAT deficiency and the apolipoproteinA-IMilano (AIM) variant. AIM has a cysteine for arginine at position 173 in the otherwise cyste...
journal_title：Pharmacological research
pub_type： 杂志文章,随机对照试验
doi：10.1016/j.phrs.2016.05.001
更新日期：2016-09-01 00:00:00
abstract：:Hepatitis E virus (HEV) is the most common cause of viral hepatitis worldwide. Genotypes 1 and 2 (GT1 and GT2) are mainly present in developing countries, while GT3 and GT4 are prevalent in developed and high-income countries. In the majority of cases, HEV causes a self-limiting hepatitis. GT3 and GT4 can be responsib...
journal_title：Pharmacological research
pub_type： 杂志文章,评审
doi：10.1016/j.phrs.2018.02.030
更新日期：2018-04-01 00:00:00
abstract：:Dyslipidemia and hyperglycemia are associated with an increased risk of ischemic cardiovascular disease. Positive effects of a nutraceutical combination comprising red yeast rice, berberine, policosanol, astaxanthin, coenzyme Q10 and folic acid (NComb) on plasma lipid and glucose levels have been reported in some but ...
journal_title：Pharmacological research
pub_type： 杂志文章,meta分析,评审
doi：10.1016/j.phrs.2016.04.021
更新日期：2016-08-01 00:00:00
