bluuebunny/crossref_metadata_2025 huggingface dataset:
THE PROTECTIVE EFFECT OF THE CARTHMUS TINCTORIUS LEAVES EXTRACTON METHOTREXATE-INDUCED PULMONARY FIBROSIS IN RATS
Authors: KHADHEM HANAA SALMAN , MTHUWAINI MAHDI , MAJID WAJDY J.
Published: September 2019

Objective: Pulmonary fibrosis (PF) is an irreversible and untreatable human disease encompasses a large group of chronic lung disorders associated with excessive remodeling, scarring, and fibrosis.

The current work was designed to study the harmful effects of methotrexate (MTX) administration on the lung and the possible protective role of Carthmus tinctorius leaves extract. The animals were utilized in this study.

Methods: A total of 40 male healthy adult Wistar albino rats with anaverage body weight of 200±25 g, were divided into four groups (10 animals each). G1: control group, G2: MTX group, G3: Carthamus tinctorius (CT), group G4:MTX+Carthamus tinctorius(CT). CT was administered orally at a dose of (40 mg/kg/day) for 4 w to G3 and G4. The (CT) group were performed to explore any toxic effect of the (CT) extract on the lung. Rats of G2 and G4 administered 4 mg/kg dose of MTX orally for 28 d. Rats of G1 were intraperitoneally (i. p) administered with normal saline 0.5 ml ∕ day for four weeks (4wk) to serveas control. The animals were weighed at the beginning, though, and at the end of experiments.

Results: The study showed that the relative lung weight was significantly increased at (P˂0.01) in MTX-treated animals in comparison to the control group. A combination of CT extract with MTX revealed significant decrease (P<0.01) in the lung relative weight in comparison to MTX group. Histopathological examination revealed that lung injury was less severe in group 3 and 4compared to group 2. The results indicated that CT significantly decreased collagen deposition, hydroxyproline content, and ameliorated pathological changes.

Conclusion: The study has clearly identified the importance protective role of CT extract on pulmonary fibrosis induced by methoxerate. We recommended CT as one of therapeutic strategy to amelioratethe lung fibrosis associated with methotrexate therapy.
Effectiveness of using an extensively hydrolyzed casein formula supplemented with
Lactobacillus rhamnosus
GG compared with an extensively hydrolysed whey formula in managing cow’s milk protein allergic infants
Authors: Guest Julian F , Fuller Graham W
Published: September 2019

Aim:
To assess the comparative effectiveness of two hypoallergenic formulae in managing cow’s milk allergic infants.
Materials & methods:
This study retrospectively analyzed the case records of 940 formula-fed cow’s milk allergic infants in the UK extracted from The Health Improvement Network database.
Results:
At 24 months after starting a formula, 77% of infants fed an extensively hydrolyzed casein formula supplemented with
Lactobacillus rhamnosus
GG (eHCF LGG; n = 470) were estimated to have been successfully managed compared with 63% of matched infants who were fed an extensively hydrolyzed whey formula (eHWF; n = 470; p < 0.001). Additionally, significantly more eHWF-fed infants were estimated to be experiencing gastrointestinal symptoms, eczema and asthma (7.1 vs 3.1%; p < 0.02) at 24 months.
Conclusion:
First-line management of newly diagnosed cow’s milk allergic infants with eHCF LGG may slow down the allergic march seen in cow’s milk allergic children.
Lanosterol biosynthesis pathway (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Authors: Benson Helen E.
Published: September 2019

Lanosterol is a precursor for cholesterol, which is synthesized primarily in the liver in a pathway often described as the mevalonate or HMG-CoA reductase pathway. The first two steps (formation of acetoacetyl CoA and the mitochondrial generation of (S)-3-hydroxy-3-methylglutaryl-CoA) are also associated with oxidation of fatty acids.
Cannabinoid receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Authors: Abood Mary , Alexander Stephen P.H. , Barth Francis , Bonner Tom I. , Bradshaw Heather , Cabral Guy , Casellas Pierre , Cravatt Ben F. , Devane William A. , Di Marzo Vincenzo , Elphick Maurice R. , Felder Christian C. , Greasley Peter , Herkenham Miles , Howlett Allyn C. , Kunos George , Mackie Ken , Mechoulam Raphael , Pertwee Roger G. , Ross Ruth A.
Published: September 2019

Cannabinoid receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Cannabinoid Receptors [107]) are activated by endogenous ligands that include N-arachidonoylethanolamine (anandamide), N-homo-γ-linolenoylethanolamine, N-docosatetra-7,10,13,16-enoylethanolamine and 2-arachidonoylglycerol. Potency determinations of endogenous agonists at these receptors are complicated by the possibility of differential susceptibility of endogenous ligands to enzymatic conversion [4].There are currently three licenced cannabinoid medicines each of which contains a compound that can activate CB1 and CB2 receptors [104]. Two of these medicines were developed to suppress nausea and vomiting produced by chemotherapy. These are nabilone (Cesamet®), a synthetic CB1/CB2 receptor agonist, and synthetic Δ9-tetrahydrocannabinol (Marinol®; dronabinol), which can also be used as an appetite stimulant. The third medicine, Sativex®, contains mainly Δ9-tetrahydrocannabinol and cannabidiol, both extracted from cannabis, and is used to treat multiple sclerosis and cancer pain.
ABCA subfamily (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Authors: Vore Mary
Published: September 2019

To date, 12 members of the human ABCA subfamily are identified. They share a high degree of sequence conservation and have been mostly related with lipid trafficking in a wide range of body locations. Mutations in some of these genes have been described to cause severe hereditary diseases related with lipid transport, such as fatal surfactant deficiency or harlequin ichthyosis. In addition, most of them are hypothesized to participate in the subcellular sequestration of drugs, thereby being responsible for the resistance of several carcinoma cell lines against drug treatment [1].
ABCC subfamily (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Authors: Vore Mary
Published: September 2019

Subfamily ABCC contains thirteen members and nine of these transporters are referred to as the Multidrug Resistance Proteins (MRPs). The MRP proteins are found throughout nature and they mediate many important functions. They are known to be involved in ion transport, toxin secretion, and signal transduction [5].
ABCG subfamily (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Authors: Kerr Ian
Published: September 2019

This family of 'half-transporters' act as homo- or heterodimers; particularly ABCG5 and ABCG8 are thought to be obligate heterodimers. The ABCG5/ABCG heterodimer sterol transporter structure has been determined [4], suggesting an extensive intracellular nucleotide binding domain linked to the transmembrane domains by a fold in the primary sequence. The functional ABCG2 transporter appears to be a homodimer with structural similarities to the ABCG5/ABCG8 heterodimer [7].
Dopamine receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Authors: Beaulieu Jean-Martin , Borrelli Emiliana , Carlsson Arvid , Caron Marc G. , Civelli Olivier , Espinoza Stefano , Fisone Gilberto , Gainetdinov Raul R. , Grandy David K. , Kebabian John W. , Langer Saloman Z. , Missale Maria Cristina , Neve Kim A. , Scatton Bernard , Schwartz Jean-Charles , Sedvall Goran , Seeman Philip , Sibley David R. , Sokoloff Pierre , Spano Pierre F. , Van Tol Hubert H. M.
Published: September 2019

Dopamine receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Dopamine Receptors [363]) are commonly divided into D1-like (D1 and D5) and D2-like (D2, D3 and D4) families, where the endogenous agonist is dopamine.
SLC27 family of fatty acid transporters (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Authors: Stahl Andreas
Published: September 2019

Fatty acid transporter proteins (FATPs) are a family (SLC27) of six transporters (FATP1-6). They have at least one, and possibly six [4, 11], transmembrane segments, and are predicted on the basis of structural similarities to form dimers. SLC27 members have several structural domains: integral membrane associated domain, peripheral membrane associated domain, FATP signature, intracellular AMP binding motif, dimerization domain, lipocalin motif, and an ER localization domain (identified in FATP4 only) [2, 8, 9]. These transporters are unusual in that they appear to express intrinsic very long-chain acyl-CoA synthetase (EC 6.2.1.- , EC 6.2.1.7) enzyme activity. Within the cell, these transporters may associate with plasma and peroxisomal membranes. FATP1-4 and -6 transport long- and very long-chain fatty acids, while FATP5 transports long-chain fatty acids as well as bile acids [7, 11].
G protein-coupled estrogen receptor (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Authors: Filardo Edward , Neubig Richard , Prossnitz Eric R.
Published: September 2019

The G protein-coupled estrogen receptor (GPER, nomenclature as agreed by the NC-IUPHAR Subcommittee on the G protein-coupled estrogen receptor [24]) was identified following observations of estrogen-evoked cyclic AMP signalling in breast cancer cells [2], which mirrored the differential expression of an orphan 7-transmembrane receptor GPR30 [5]. There are observations of both cell-surface and intracellular expression of the GPER receptor [27, 32]. Selective agonist/ antagonists for GPER have been characterized [24]. Antagonists of the nuclear estrogen receptor, such as fulvestrant [10], tamoxifen [27, 32] and raloxifene [23], as well as the flavonoid 'phytoestrogens' genistein and quercetin [16], are agonists of GPER. A complete review of GPER pharmacology has been recently published [24]. The roles of GPER in physiological systems throughout the body (cardiovascular, metabolic, endocrine, immune, reproductive) and in cancer have also been reviewed [24, 25, 18, 15, 8].
SLC47 family of multidrug and toxin extrusion transporters (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Authors: Inui Ken-ichi
Published: September 2019

These proton:organic cation exchangers are predicted to have 13 TM segments [10] and are suggested to be responsible for excretion of many drugs in the liver and kidneys.
SLCO family of organic anion transporting polypeptides (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Authors: Hagenbuch Bruno
Published: September 2019

The SLCO superfamily is comprised of the organic anion transporting polypeptides (OATPs). The 11 human OATPs are divided into 6 families and ten subfamilies based on amino acid identity. These proteins are located on the plasma membrane of cells throughout the body. They have 12 TM domains and intracellular termini, with multiple putative glycosylation sites. OATPs mediate the sodium-independent uptake of a wide range of amphiphilic substrates, including many drugs and toxins. Due to the multispecificity of these proteins, this guide lists classes of substrates and inhibitors for each family member. More comprehensive lists of substrates, inhibitors, and their relative affinities may be found in the review articles listed below.
Class Frizzled GPCRs (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Authors: Arthofer Elisa , Dijksterhuis Jacomijn , Hot Belma , Kozielewicz Paweł , Lauth Matthias , Olofsson Jessica , Petersen Julian , Polonio Tilman , Schulte Gunnar , Strakova Katerina , Valnohova Jana , Wright Shane
Published: September 2019

Receptors of the Class Frizzled (FZD, nomenclature as agreed by the NC-IUPHAR subcommittee on the Class Frizzled GPCRs [156]), are GPCRs originally identified in Drosophila [17], which are highly conserved across species. While SMO shows structural resemblance to the 10 FZDs, it is functionally separated as it mediates effects in the Hedgehog signaling pathway [156]. FZDs are activated by WNTs, which are cysteine-rich lipoglycoproteins with fundamental functions in ontogeny and tissue homeostasis. FZD signalling was initially divided into two pathways, being either dependent on the accumulation of the transcription regulator β-catenin or being β-catenin-independent (often referred to as canonical vs. non-canonical WNT/FZD signalling, respectively). WNT stimulation of FZDs can, in cooperation with the low density lipoprotein receptors LRP5 (O75197) and LRP6 (O75581), lead to the inhibition of a constitutively active destruction complex, which results in the accumulation of β-catenin and subsequently its translocation to the nucleus. β-Catenin, in turn, modifies gene transcription by interacting with TCF/LEF transcription factors. β-Catenin-independent FZD signalling is far more complex with regard to the diversity of the activated pathways. WNT/FZD signalling can lead to the activation of heterotrimeric G proteins [28, 159, 135], the elevation of intracellular calcium [164], activation of cGMP-specific PDE6 [2] and elevation of cAMP as well as RAC-1, JNK, Rho and Rho kinase signalling [48]. Novel resonance energy transfer-based tools have allowed the study of the GPCR-like nature of FZDs in greater detail. Upon ligand stimulation, FZDs undergo conformational changes and signal via heterotrimeric G proteins [213, 214]. Furthermore, the phosphoprotein Dishevelled constitutes a key player in WNT/FZD signalling. Importantly, FZDs exist in at least two distinct conformational states that regulate the pathway selection [214]. As with other GPCRs, members of the Frizzled family are functionally dependent on the arrestin scaffolding protein for internalization [19], as well as for β-catenin-dependent [12] and -independent [80, 13] signalling. The pattern of cell signalling is complicated by the presence of additional ligands, which can enhance or inhibit FZD signalling (secreted Frizzled-related proteins (sFRP), Wnt-inhibitory factor (WIF), sclerostin or Dickkopf (DKK)), as well as modulatory (co)-receptors with Ryk, ROR1, ROR2 and Kremen, which may also function as independent signalling proteins.
Nitric oxide synthases (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Authors: Billiar Timothy R. , Cirino Giuseppe , Fulton David , Motterlini Roberto , Papapetropoulos Andreas , Szabo Csaba
Published: September 2019

Nitric oxide synthases (NOS, E.C. 1.14.13.39) are a family of oxidoreductases that synthesize nitric oxide (NO.) via the NADPH and oxygen-dependent consumption of L-arginine with the resultant by-product, L-citrulline. There are 3 NOS isoforms and they are related by their capacity to produce NO, highly conserved organization of functional domains and significant homology at the amino acid level. NOS isoforms are functionally distinguished by the cell type where they are expressed, intracellular targeting and transcriptional and post-translation mechanisms regulating enzyme activity. The nomenclature suggested by NC-IUPHAR of NOS I, II and III [11] has not gained wide acceptance, and the 3 isoforms are more commonly referred to as neuronal NOS (nNOS), inducible NOS (iNOS) and endothelial NOS (eNOS) which reflect the location of expression (nNOS and eNOS) and inducible expression (iNOS). All are dimeric enzymes that shuttle electrons from NADPH, which binds to a C-terminal reductase domain, through the flavins FAD and FMN to the oxygenase domain of the other monomer to enable the BH4-dependent reduction of heme bound oxygen for insertion into the substrate, L-arginine. Electron flow from reductase to oxygenase domain is controlled by calmodulin binding to canonical calmodulin binding motif located between these domains. eNOS and nNOS isoforms are activated at concentrations of calcium greater than 100 nM, while iNOS shows higher affinity for Ca2+/calmodulin with great avidity and is essentially calcium-independent and constitutively active. Efficient stimulus-dependent coupling of nNOS and eNOS is achieved via subcellular targeting through respective N-terminal PDZ and fatty acid acylation domains whereas iNOS is largely cytosolic and function is independent of intracellular location. nNOS is primarily expressed in the brain and neuronal tissue, iNOS in immune cells such as macrophages and eNOS in the endothelial layer of the vasculature although exceptions in other cells have been documented. L-NAME and related modified arginine analogues are inhibitors of all three isoforms, with IC50 values in the micromolar range.
Phosphodiesterases, 3',5'-cyclic nucleotide (PDEs) (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Authors: Yan Chen
Published: September 2019

3',5'-Cyclic nucleotide phosphodiesterases (PDEs, 3',5'-cyclic-nucleotide 5'-nucleotidohydrolase), E.C. 3.1.4.17, catalyse the hydrolysis of a 3',5'-cyclic nucleotide (usually cyclic AMP or cyclic GMP). isobutylmethylxanthine is a nonselective inhibitor with an IC50 value in the millimolar range for all isoforms except PDE 8A, 8B and 9A. A 2',3'-cyclic nucleotide 3'-phosphodiesterase (E.C. 3.1.4.37 CNPase) activity is associated with myelin formation in the development of the CNS.
Hydrogen sulphide synthesis (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Authors: Billiar Timothy R. , Cirino Giuseppe , Fulton David , Motterlini Roberto , Papapetropoulos Andreas , Szabo Csaba
Published: September 2019

Hydrogen sulfide is a gasotransmitter, with similarities to nitric oxide and carbon monoxide. Although the enzymes indicated below have multiple enzymatic activities, the focus here is the generation of hydrogen sulphide (H2S) and the enzymatic characteristics are described accordingly. Cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) are pyridoxal phosphate (PLP)-dependent enzymes. 3-mercaptopyruvate sulfurtransferase (3-MPST) functions to generate H2S; only CAT is PLP-dependent, while 3-MPST is not. Thus, this third pathway is sometimes referred to as PLP-independent. CBS and CSE are predominantly cytosolic enzymes, while 3-MPST is found both in the cytosol and the mitochondria. For an authoritative review on the pharmacological modulation of H2S levels, see Szabo and Papapetropoulos, 2017 [4].
Glucagon receptor family (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Authors: Bataille Dominique , Chan Susan L. , Delagrange Philippe , Drucker Daniel J. , Göke Burkhard , Hills Rebecca , Mayo Kelly E. , Miller Laurence J. , Salvatori Roberto , Thorens Bernard
Published: September 2019

The glucagon family of receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on the Glucagon receptor family [159]) are activated by the endogenous peptide (27-44 aa) hormones glucagon, glucagon-like peptide 1, glucagon-like peptide 2, glucose-dependent insulinotropic polypeptide (also known as gastric inhibitory polypeptide), GHRH and secretin. One common precursor (GCG) generates glucagon, glucagon-like peptide 1 and glucagon-like peptide 2 peptides [116]. For a recent review on review the current understanding of the structures of GLP-1 and GLP-1R, the molecular basis of their interaction, and the signaling events associated with it, see de Graaf et al., 2016 [87].
Tumour necrosis factor (TNF) receptor family (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Authors: MacEwan David
Published: September 2019

Dysregulated TNFR signalling is associated with many inflammatory disorders, including some forms of arthritis and inflammatory bowel disease, and targeting TNF has been an effective therapeutic strategy in these diseases and for cancer immunotherapy [4, 5, 38].
Lysophospholipid (LPA) receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Authors: Blaho Victoria , Chun Jerold , Frantz Aaron , Hla Timothy , Jones Danielle , Jonnalagadda Deepa , Kihara Yasuyuki , Mizuno Hirotaka , Moolenaar Wouter , Mpamhanga Chido , Spiegel Sarah , Tan Valerie , Yung Yun C.
Published: September 2019

Lysophosphatidic acid (LPA) receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Lysophospholipid Receptors [50, 18]) are activated by the endogenous phospholipid LPA. The first receptor, LPA1, was identified as ventricular zone gene-1 (vzg-1) [38], leading to deorphanisation of members of the endothelial differentiation gene (edg) family as other LPA receptors along with sphingosine 1-phosphate (S1P) receptors. Additional LPA receptor GPCRs were later identified. Gene names have been codified as LPAR1, etc. to reflect the receptor function of proteins. The crystal structure of LPA1 was solved and demonstrates extracellular LPA access to the binding pocket, consistent with proposed delivery via autotaxin [12]. These studies have also implicated cross-talk with endocannabinoids via phosphorylated intermediates that can also activate these receptors. The identified receptors can account for most, although not all, LPA-induced phenomena in the literature, indicating that a majority of LPA-dependent phenomena are receptor-mediated. Binding affinities of unlabeled, natural LPA and AEAp to LPA1 were measured using backscattering interferometry (pKd = 9) [73]. Binding affinities were 77-fold lower than than values obtained using radioactivity [111]. Targeted deletion of LPA receptors has clarified signalling pathways and identified physiological and pathophysiological roles. Independent validation by multiple groups has been reported in the peer-reviewed literature for all six LPA receptors described in the tables, including further validation using a distinct read-out via a novel TGFα "shedding" assay [45]. LPA has also been described as an agonist for the transient receptor potential (Trp) ion channel TRPV1 [76] and TRPA1 [53]. LPA was originally proposed to be a ligand for GPCR35, but data show that in fact it is a receptor for CXCL17 [68]. All of these proposed non-GPCR receptor identities require confirmation and are not currently recognized as bona fide LPA receptors.
Melatonin receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Authors: Cardinali Daniel P. , Delagrange Philippe , Dubocovich Margarita L. , Jockers Ralf , Krause Diana N. , Markus Regina Pekelmann , Olcese James , Pintor Jesús , Renault Nicolas , Sugden David , Tosini Gianluca , Zlotos Darius Paul
Published: September 2019

Melatonin receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Melatonin Receptors [36]) are activated by the endogenous ligands melatonin and clinically used drugs like ramelteon, agomelatine and tasimelteon.
Oxoglutarate receptor (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Authors: Davenport Anthony P. , Liew Wen Chiy
Published: September 2019

Nomenclature as recommended by NC-IUPHAR [2].
Neuropeptide W/neuropeptide B receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Authors: Davenport Anthony P. , Maguire Janet J. , Singh Gurminder
Published: September 2019

The neuropeptide BW receptor 1 (NPBW1, provisional nomenclature [5]) is activated by two 23-amino-acid peptides, neuropeptide W (neuropeptide W-23) and neuropeptide B (neuropeptide B-23) [20, 6]. C-terminally extended forms of the peptides (neuropeptide W-30 and neuropeptide B-29) also activate NPBW1 [2]. Unique to both forms of neuropeptide B is the N-terminal bromination of the first tryptophan residue, and it is from this post-translational modification that the nomenclature NPB is derived. These peptides were first identified from bovine hypothalamus and therefore are classed as neuropeptides. Endogenous variants of the peptides without the N-terminal bromination, des-Br-neuropeptide B-23 and des-Br-neuropeptide B-29, were not found to be major components of bovine hypothalamic tissue extracts. The NPBW2 receptor is activated by the short and C-terminal extended forms of neuropeptide W and neuropeptide B [2].
Prostanoid receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Authors: Breyer Richard M. , Clapp Lucie , Coleman Robert A. , Giembycz Mark , Heinemann Akos , Hills Rebecca , Jones Robert L. , Narumiya Shuh , Norel Xavier , Pettipher Roy , Sugimoto Yukihiko , Woodward David F. , Yao Chengcan
Published: September 2019

Prostanoid receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Prostanoid Receptors [644]) are activated by the endogenous ligands prostaglandins PGD2, PGE1, PGE2 , PGF2α, PGH2, prostacyclin [PGI2] and thromboxane A2. Measurement of the potency of PGI2 and thromboxane A2 is hampered by their instability in physiological salt solution; they are often replaced by cicaprost and U46619, respectively, in receptor characterization studies.
Proteinase-activated receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Authors: Bunnett Nigel , DeFea Kathryn , Hamilton Justin , Hollenberg Morley D. , Ramachandran Rithwik , Trejo JoAnn
Published: September 2019

Proteinase-activated receptors (PARs, nomenclature as agreed by the NC-IUPHAR Subcommittee on Proteinase-activated Receptors [35]) are unique members of the GPCR superfamily activated by proteolytic cleavage of their amino terminal exodomains. Agonist proteinase-induced hydrolysis unmasks a tethered ligand (TL) at the exposed amino terminus, which acts intramolecularly at the binding site in the body of the receptor to effect transmembrane signalling. TL sequences at human PAR1-4 are SFLLRN-NH2, SLIGKV-NH2, TFRGAP-NH2 and GYPGQV-NH2, respectively. With the exception of PAR3, synthetic peptides with these sequences (as carboxyl terminal amides) are able to act as agonists at their respective receptors. Several proteinases, including neutrophil elastase, cathepsin G and chymotrypsin can have inhibitory effects at PAR1 and PAR2 such that they cleave the exodomain of the receptor without inducing activation of Gαq-coupled calcium signalling, thereby preventing activation by activating proteinases but not by agonist peptides. Neutrophil elastase (NE) cleavage of PAR1 and PAR2 can however activate MAP kinase signaling by exposing a TL that is different from the one revealed by trypsin [73]. PAR2 ectivation by NE regulates inflammation and pain responses [101, 65] and triggers mucin secretion from airway epithelial cells [102].
Relaxin family peptide receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Authors: Bathgate Ross , Dschietzig Thomas , Gundlach Andrew L. , Halls Michelle , Summers Roger
Published: September 2019

Relaxin family peptide receptors (RXFP, nomenclature as agreed by the NC-IUPHAR Subcommittee on Relaxin family peptide receptors [18, 75]) may be divided into two pairs, RXFP1/2 and RXFP3/4. Endogenous agonists at these receptors are heterodimeric peptide hormones structurally related to insulin: relaxin-1, relaxin, relaxin-3 (also known as INSL7), insulin-like peptide 3 (INSL3) and INSL5. Species homologues of relaxin have distinct pharmacology and relaxin interacts with RXFP1, RXFP2 and RXFP3, whereas mouse and rat relaxin selectively bind to and activate RXFP1 [172]. relaxin-3 is the ligand for RXFP3 but it also binds to RXFP1 and RXFP4 and has differential affinity for RXFP2 between species [170]. INSL5 is the ligand for RXFP4 but is a weak antagonist of RXFP3. relaxin and INSL3 have multiple complex binding interactions with RXFP1 [176] and RXFP2 [84] which direct the N-terminal LDLa modules of the receptors together with a linker domain to act as a tethered ligand to direct receptor signaling [173]. INSL5 and relaxin-3 interact with their receptors using distinct residues in their B-chains for binding, and activation, respectively [211, 97].
Vasopressin and oxytocin receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Authors: Bichet Daniel , Bouvier Michel , Chini Bice , Gimpl Gerald , Guillon Gilles , Kimura Tadashi , Knepper Mark , Lolait Stephen , Manning Maurice , Mouillac Bernard , O'Carroll Anne-Marie , Serradeil-Le Gal Claudine , Soloff Melvyn , Verbalis Joseph G. , Wheatley Mark , Zingg Hans H.
Published: September 2019

Vasopressin (AVP) and oxytocin (OT) receptors (nomenclature as recommended by NC-IUPHAR [92]) are activated by the endogenous cyclic nonapeptides vasopressin and oxytocin. These peptides are derived from precursors which also produce neurophysins (neurophysin I for oxytocin; neurophysin II for vasopressin). Vasopressin and oxytocin differ at only 2 amino acids (positions 3 and 8). There are metabolites of these neuropeptides that may be biologically active [67].
Cyclic nucleotide-regulated channels (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Authors: Becirovic Elvir , Biel Martin , Hammelmann Verena , Hofmann Franz , Kaupp U. Benjamin
Published: September 2019

Cyclic nucleotide-gated (CNG) channels are responsible for signalling in the primary sensory cells of the vertebrate visual and olfactory systems.CNG channels are voltage-independent cation channels formed as tetramers. Each subunit has 6TM, with the pore-forming domain between TM5 and TM6. CNG channels were first found in rod photoreceptors [69, 98], where light signals through rhodopsin and transducin to stimulate phosphodiesterase and reduce intracellular cyclic GMP level. This results in a closure of CNG channels and a reduced ‘dark current’. Similar channels were found in the cilia of olfactory neurons [153] and the pineal gland [60]. The cyclic nucleotides bind to a domain in the C terminus of the subunit protein: other channels directly binding cyclic nucleotides include HCN, eag and certain plant potassium channels.Hyperpolarisation-activated, cyclic nucleotide-gated (HCN)The hyperpolarisation-activated, cyclic nucleotide-gated (HCN) channels are cation channels that are activated by hyperpolarisation at voltages negative to ~-50 mV. The cyclic nucleotides cyclic AMP and cyclic GMP directly activate the channels and shift the activation curves of HCN channels to more positive voltages, thereby enhancing channel activity. HCN channels underlie pacemaker currents found in many excitable cells including cardiac cells and neurons [56, 164]. In native cells, these currents have a variety of names, such as Ih, Iq and If. The four known HCN channels have six transmembrane domains and form tetramers. It is believed that the channels can form heteromers with each other, as has been shown for HCN1 and HCN4 [2]. High resolution structural studies of CNG and HCN channels has provided insight into the the gating processes of these channels [117, 121]. A standardised nomenclature for CNG and HCN channels has been proposed by the NC-IUPHAR subcommittee on voltage-gated ion channels [88].
Integrins (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Authors: Farndale Richard W. , Jarvis Gavin E.
Published: September 2019

Integrins are unusual signalling proteins that function to signal both from the extracellular environment into the cell, but also from the cytoplasm to the external of the cell. The intracellular signalling cascades associated with integrin activation focus on protein kinase activities, such as focal adhesion kinase and Src. Based on this association between extracellular signals and intracellular protein kinase activity, we have chosen to include integrins in the 'Catalytic receptors' section of the database until more stringent criteria from NC-IUPHAR allows precise definition of their classification.Integrins are heterodimeric entities, composed of α and β subunits, each 1TM proteins, which bind components of the extracellular matrix or counter-receptors expressed on other cells. One class of integrin contains an inserted domain (I) in its α subunit, and if present (in α1, α2, α10, α11, αD, αE, αL, αM and αX), this I domain contains the ligand binding site. All β subunits possess a similar I-like domain, which has the capacity to bind ligand, often recognising the RGD motif. The presence of an α subunit I domain precludes ligand binding through the β subunit. Integrins provide a link between ligand and the actin cytoskeleton (through typically short intracellular domains). Integrins bind several divalent cations, including a Mg2+ ion in the I or I-like domain that is essential for ligand binding. Other cation binding sites may regulate integrin activity or stabilise the 3D structure. Integrins regulate the activity of particular protein kinases, including focal adhesion kinase and integrin-linked kinase. Cellular activation regulates integrin ligand affinity via inside-out signalling and ligand binding to integrins can regulate cellular activity via outside-in signalling.Several drugs that target integrins are in clinical use including: (1) abciximab (αIIbβ3) for short term prevention of coronary thrombosis, (2) vedolizumab (α4β7) to reduce gastrointestinal inflammation, and (3) natalizumab (α4β1) in some cases of severe multiple sclerosis.
Bile acid receptor (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Authors: Bonner Tom I. , Davenport Anthony P. , Hills Rebecca , Maguire Janet J. , Rosser Edward
Published: September 2019

The bile acid receptor (GPBA) responds to bile acids produced during the liver metabolism of cholesterol. Selective agonists are promising drugs for the treatment of metabolic disorders, such as type II diabetes, obesity and atherosclerosis.
Voltage-gated sodium channels (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Authors: Catterall William A. , Goldin Alan L. , Waxman Stephen G.
Published: September 2019

Sodium channels are voltage-gated sodium-selective ion channels present in the membrane of most excitable cells. Sodium channels comprise of one pore-forming α subunit, which may be associated with either one or two β subunits [176]. α-Subunits consist of four homologous domains (I–IV), each containing six transmembrane segments (S1–S6) and a pore-forming loop. The positively charged fourth transmembrane segment (S4) acts as a voltage sensor and is involved in channel gating. The crystal structure of the bacterial NavAb channel has revealed a number of novel structural features compared to earlier potassium channel structures including a short selectivity filter with ion selectivity determined by interactions with glutamate side chains [268]. Interestingly, the pore region is penetrated by fatty acyl chains that extend into the central cavity which may allow the entry of small, hydrophobic pore-blocking drugs [268]. Auxiliary β1, β2, β3 and β4 subunits consist of a large extracellular N-terminal domain, a single transmembrane segment and a shorter cytoplasmic domain.The nomenclature for sodium channels was proposed by Goldin et al., (2000) [143] and approved by the NC-IUPHAR Subcommittee on sodium channels (Catterall et al., 2005, [51]).
3.6.5.2 Small monomeric GTPases (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Authors: Faccenda Elena
Published: September 2019

Small G-proteins, are a family of hydrolase enzymes that can bind and hydrolyze guanosine triphosphate (GTP). They are a type of G-protein found in the cytosol that are homologous to the alpha subunit of heterotrimeric G-proteins, but unlike the alpha subunit of G proteins, a small GTPase can function independently as a hydrolase enzyme to bind to and hydrolyze a guanosine triphosphate (GTP) to form guanosine diphosphate (GDP). The best-known members are the Ras GTPases and hence they are sometimes called Ras subfamily GTPases.
2A. Hepatocyte nuclear factor-4 receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Authors: Sladek Frances M.
Published: September 2019

The nomenclature of hepatocyte nuclear factor-4 receptors is agreed by the NC-IUPHAR Subcommittee on Nuclear Hormone Receptors [8]. While linoleic acid has been identified as the endogenous ligand for HNF4α its function remains ambiguous [73]. HNF4γ has yet to be paired with an endogenous ligand.
3A. Estrogen receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
Authors: Coons Laurel , Korach Kenneth S.
Published: September 2019

Estrogen receptor (ER) activity regulates diverse physiological processes via transcriptional modulation of target genes. The selection of target genes and the magnitude of the response, be it induction or repression, are determined by many factors, including the effect of the hormone ligand and DNA binding on ER structural conformation, and the local cellular regulatory environment. The cellular environment defines the specific complement of DNA enhancer and promoter elements present and the availability of coregulators to form functional transcription complexes. Together, these determinants control the resulting biological response.
EL "ESTADO PROVIDENCIA" Y LA CRITICA NEOLIBERAL.
Authors: Perrotini H Ignacio , Vega L. Eduardo
Published: September 2019

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UN PARTIDO DE ESTADO EN SU HISTORIA RECIENTE. RETROSPECTIVA Y PERSPECTIVA DE LA XII ASAMBLEA DEL PRI.
Authors: Xelhuantzi López María
Published: September 2019

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Cronología de las principales reformas a la legislación electoral de México (1910-1994).
Authors: SIRVENT GUITÉRREZ Carlos
Published: September 2019

En este trabajo se muestra una cronología de las principales reformas a la legislación electoral en México durante el periodo 1910-1994.
Reflexiones sobre la violencia.
Authors: KEANE John , ALARCÓN OLGUÍN Víctor
Published: September 2019

Este es un extracto del libro Reflections on violence (en prensa) a ser publicado en Inglaterra por la editorial Verso. Tomado de CSA Bulletin, otoño 1995, vol. 3, núm. 1, p. 9. Traducción de Víctor Alarcón Olguín.
La retórica de la reacción: los usos del discurso político en México.
Authors: CANSINO ORTIZ César
Published: September 2019

El objetivo de este artículo es examinar los usos de orden simbólico del discurso político en México. En particular, se consideran aquí los argumentos que desde las esferas del poder se han construido durante los últimos años con respecto a la transición democrática. El estudio pone particular interés en lo que la literatura especializada ha denominado las "retóricas de la intransigencia" ; es decir, en aquellos argumentos aparentemente racionales y neutrales pero que esconden intenciones claramente ideológicas y tendenciosas.
Latinoamérica: hacia una nueva forma de hacer política.
Authors: LE CLERQ Juan Antonio
Published: September 2019

En el presente artículo se analiza, por medio de dos principales ejes, la economía y la política, la transición de los regímenes políticos y los modelos económicos en los gobiernos de América Latina. El paso de las dictaduras militares a la participación política civil trajo consigo la aplicación de diversos modelos económicos que resultaron en endeudamiento, inflación y diversos problemas económicos y políticos como la legitimidad y la participación de partidos y organismos siempre de la mano de la institucionalización en bien del orden.
Liberalismo y posmodernidad.
Authors: FAVELA GAVIA Alejandro , CALVILLO VELASCO Miriam
Published: September 2019

Artículo analítico donde, desde una perspectiva teórica, se aborda (a partir de una crítica lógica de los postulados del liberalismo) y se discuten las posibilidades de cambio que poseen los sistemas políticos contemporáneos tomando en cuanta características como pluralidad y globalización, organización ciudadana, diversidad cultural y consensos traslucidos.
Las culturas políticas y su análisis: una perspectiva.
Authors: VALLÍN MEDINA Roberto
Published: September 2019

A lo largo de los años ochenta se evidenció la crisis de la visión y de los presupuestos que sustentaban el universalismo en el ámbito de las ciencias sociales. A este propósito, el campo de la política comparada, en el que se inscribe el análisis de las culturas políticas, no ha sido la excepción; de tal suerte, el hecho se ha traducido en la renovación de los paradigmas de la ciencia política. Es en este tema que repara el presente artículo.
De Quincey. El asesinato como arte y la vida como valor.
Authors: PINEDA JIMÉNEZ Humberto
Published: September 2019

El artículo biográfico de Tomás de Quincey desarrolla su obra Del asesinato considerado como una de las bellas artes, dilucidando la vida como valor como premisa. Asimismo explora la trasgresión referencial al valor y a la moral.
La alteridad en Iván Ilich.
Authors: OLVERA GÓMEZ Rosa María , MÁRQUEZ MUÑOZ Jorge Federico
Published: September 2019

Este artículo comienza con las notas biográficas de Iván Ilich pues es el medio perfecto de diálogo y entendimiento de la obra y perspectiva de este personaje. Sus aportaciones para el entendimiento de América Latina, sus estudios van desde la historia del agua, la memora , el texto, hasta una crítica feroz de la sociedad industrial. Sin embargo, se pueden encontrar dos puntos constantes; el camino histórico y su respeto por el otro. Este trabajo desarrolla con mayor profundidad la reflexión de su obra La sociedad desescolarizada, donde encuentra un mal en la manipulación que se ejerce en el sistema escolarizado.
Reforma del Estado: límites y perspectivas.
Authors: RODRÍGUEZ ARAUJO Octavio
Published: September 2019

Este trabajo comienza cuestionando las implicaciones de la denominación "Reforma del Estado", desde su distinción empírica y teórica, hasta los propósitos e implicaciones en el ámbito político.
La democracia y sus valores.
Authors: VALDÉZ ZEPEDA Andrés
Published: September 2019

El ensayo trata de contribuir al análisis de la cultura política de la sociedad mexicana, estudiando el proceso de formación y transmisión de valores en el ámbito socio-político. En especial, el trabajo abordar el análisis de la familia, la escuela, la iglesia, los medios de comunicación y las organizaciones político-sociales de México, como instituciones importantes en la formación y transmisión de valores políticos. Finalmente, se concluye que un tránsito verdadero a la democracia implica no sólo cambios en materia de normas y leyes, sino transformaciones sustantivas en las instituciones básicas de la sociedad.
Mujeres de ayer: participación política femenina en México 1910-1960.
Authors: RAMOS ESCANDÓN Carmen
Published: September 2019

Este artículo trata de la relación entre el movimiento de mujeres y el Estado en México entre 1910 y 1960. La autora afirma que el momento más importante del movimiento de mujeres en México fue en los años treinta con la creación del Frente Único Pro Derechos de la Mujer, que esgrimía el derecho al voto femenino como su demanda más importante. A pesar de haber sido discutido en la Cámara de Diputados, el voto femenino no fue aprobado en 1938 debido a las políticas anti femeninas y conservadoras del partido en el poder. Para 1953 cuando el partido oficial está bien establecido en el poder, el voto de la mujer fue aprobado, puesto que el temor de un voto femenino disidente y favorable a la Iglesia había ya desaparecido.
Crítica y utopía en el pensamiento de Emmanuel Lévinas.
Authors: MONDRAGÓN GONZÁLEZ Araceli
Published: September 2019

El pensamiento de Emmanuel Lévinas propone una nueva "socialidad", fundada en la ética, aunque no ennun discurso ético marcado por los límites de un "yo soberano" o una "racionalidad abstracta". Lévinas propone una ética fundamental de la que deriva la condición humana; a partir de una relación responsable con el otro. Este planteamiento nos advierte del peligro de circunscribir todo al Estado y nos propone una crítica desde la ética, que nos permite replantear la posibilidad de la utopía y su "sin lugar" en el horizonte de lo establecido; y rescatar, al mismo tiempo, el carácter crítico de las utopías.
Poder y zurdería.
Authors: GIL CARRASCO Félix , SUBIRATS SILVESTRE Sonia
Published: September 2019

Este trabajo realiza un acercamiento a la pregunta qué es un zurdo y sus implicaciones en el ejercicio del poder, desde los actos cotidianos que implican el desarrollo de ciertas capacidades, hasta la exclusión y discriminación de las que son sujeto los zurdos. El artículo ahonda en el sustento fisiológico y social para explicar sus vicisitudes.
El debate político e intelectual en México.
Authors: ZAMITIZ GAMBOA Héctor
Published: September 2019

Ponencia presentada en el ciclo de mesas redondas "Instituciones, democracia y mercado", organizado por la Coordinación de Ciencia Política, con motivo de los 45 años de la ciencia política en México, FCPyS, UNAM, 13 de noviembre de 1996.
Competencia electoral: recursos y equidad.
Authors: MIRÓN LINCE Rosa María
Published: September 2019

El presente artículo muestra la génesis y desarrollo del proceso electoral en materia de recursos y equidad. La forma en que se ha hecho más equitativas las condiciones de la competencia electoral.
El mito en el pensamiento europeo de los siglos XVIII y XIX.
Authors: MÁRQUEZ MUÑOZ Jorge Federico
Published: September 2019

En este texto se intentan describir y analizar los orígenes del estudio ilustrado o moderno de los mitos. Se habla de quienes inventaron dicho estudio y de los objetivos que perseguían con ello. Una vez realizada tal descripción, el texto nos invita a la siguiente reflexión: ?Cuáles son los límites de una ciencia que estudia los mitos?
El regreso de los generales. Un análisis del proceso de militarización y sus efectos sobre la transición política en México.
Authors: VALDÉZ ZEPEDA Andrés
Published: September 2019

El presente trabajo analiza los cambios en las relaciones cívico-militares que se han dado en México en los últimos ocho años. Se parte de la identificación de los cinco factores que más han influido en el proceso de fortalecimiento y modernización de la institución armada. Posteriormente, se analizan las repercusiones que la militarización puede traer sobre el proceso de transición política. Y, finalmente, se advierte de los riesgos que implica un mayor debilitamiento y de gradación de las instituciones cívico-políticas del país.
Los derechos económicos y sociales: una perspectiva histórica.
Authors: ROQUEÑÍ IBARGÜENGOITIA María del Carmen
Published: September 2019

A cincuenta años de la Declaración Universal de los Derechos Humanos se hace necesario reflexionar sobre la vigencia de éstos. Este trabajo es una revisión sobre el origen y evolución histórica de los derechos económicos y sociales. Éstos no son consustanciales a las democracias liberales. La presión de los actores y fenómenos socio-políticos fueron fundamentales para la instrumentación de políticas sociales que hicieran efectivos estos derechos.
Comunicación política.
Authors: SINGER SOCHET Martha
Published: September 2019

Texto presentado en la "Semana de la Ciencia Política", FCPyS, UNAM, abril de 1998.
La democracia en la política exterior norteamericana.
Authors: BAENA PAZ Guillermina
Published: September 2019

Traducción y comentarios a los artículos "The Rise of Illiberal Democracy", "Defending Democracy" y "Liberalism and Democracy" en Foreing Affairs 1997-1998.
Presentación
Authors: LINCE CAMPILLO Rosa María , FLORES SANTIAGO María Margarita
Published: September 2019

Presentación
El sedimento cultural mexicano.
Authors: ZAVALA ECHAVARRÍA Iván
Published: September 2019

Tomando en cuenta un trabajo previo, en este artículo se muestran dos conclusiones más a partir de un análisis estadístico por demás interesante, sobre la Encuesta Nacional de Valores realizada en 1982-1983.
Sustento y propuesta de la nueva administración pública.
Authors: UVALLE BERRONES Ricardo
Published: September 2019

El presente trabajo se concentra en dos objetivos. Uno de ellos consiste en posponer una aproximación conceptual de la reforma de gobierno tomando en consideración los trabajos principales dedicados a la gerencia pública: el otro se refiere a los escenarios en los que se puede llevar a cabo las reformas gubernamentales, tomando en cuenta las diversas estrategias de cambio.
La política como actividad del hombre.
Authors: BOLÍVAR MEZA Rosendo
Published: September 2019

No hay actividad humana ajena a la política, ni política que no se asocie a las diversas actividades de los hombres. Todos los problemas que se refieren a la existencia humana tiene que ver con la política, pues ésta es un principio activo, susceptible de abarcar todos los aspectos de la vida del hombre en sociedad. La actividad política se caracteriza precisamente por su universalidad y diversidad.