As with all physiologic processes, chronic wounds are associated with unique intracellular and cellular/extracellular matrix (ECM) receptor types and signalling messages. These cellular receptors mediate responses of the epidermis to provisional wound matrix and change in form and number in cases of impaired wound healing. Integrins are the major cell-surface ...

The manuscript by Zhang et al. describes a signaling pathway for repression of PDGF-Ralpha in fibroblasts.

Angiogenesis is an important step in the complex biological and molecular events leading to successful healing of dermal wounds. Among the different cellular effectors of wound angiogenesis, the role of mesenchymal stem cells (MSCs) is of current interest due to their transdifferentiation and proangiogenic potentials. Skin is richly innervated by ...

A computer-aided docking study was conducted to explore in detail the binding interactions between the structurally unlikely environmental oestrogen 4-nonylphenol (4NP) and three of its metabolites with the human oestrogen receptor alpha (hERα). Docking was done within the Schrodinger Suite 2008 using both a conventional rigid receptor with flexible ligand ...

Pallidal dopamine, GABA and the endogenous opioid peptides enkephalins have independently been shown to be important controllers of sensorimotor processes. Using in vivo microdialysis coupled to liquid chromatography-mass spectrometry and a behavioral assay, we explored the interaction between these three neurotransmitters in the rat globus pallidus. Amphetamine (3 mg/kg i.p.) ...

It is a common and widely accepted assumption that glycine and GABA are the main inhibitory transmitters in the central nervous system (CNS). But, in the past 20 years, several studies have clearly demonstrated that these amino acids can also be excitatory in the immature central nervous system. In addition, it ...

The identification of two novel series of formyl peptide receptor 1 (FPR1) antagonists are reported, represented by methionine benzimidazole 6 and diamide 7. Both series specifically inhibited the binding of labelled fMLF to hrFPR1 and selectively antagonized FPR1 function in human neutrophils, making them useful in vitro validation tools for ...

A new water-soluble receptor 1 has been synthesized and it showed selective recognition of zwitterionic arginine in aqueous media. Moreover, the receptor 1 could be regard as a facile tool for protein labeling and quantitative determination (LOD = 15 nM).

This article reviews the role of arginine-vasopressin and the vasopressin analogue terlipressin as potent alternative vasoconstrictors in the treatment of fluid and catecholamine-refractory septic shock. Terlipressin is the most selective, clinically available V1 receptor agonist, and may be more potent than arginine-vasopressin in restoring catecholamine refractory septic shock. Recent experimental ...

Taurine, a sulfur-containing amino acid, has high hydrophilicity and is poorly absorbed. Tauropyrone, a taurine-containing 1,4-dihydropyridine derivative, is suggested to have greater activity than taurine owing to improved physicochemical properties that facilitate delivery of the compound to target cells. The aim of this study was to determine whether the 1,4-dihydropyridine ...

β₃-Adrenoceptor mRNA is expressed in the human heart, but corresponding receptor protein has not yet consistently been demonstrated. Furthermore, their physiological role remains highly controversial. For example, in human atria these receptors apparently do not promote cAMP formation. Evidence presented in this issue of the BJP suggests that a previously ...

Cation-π interactions have been demonstrated to play a major role in agonist-binding in Cys-loop receptors. However, neither the aromatic amino acid contributing to this interaction nor its location is conserved among Cys-loop receptors. Likewise, it is not clear how many different agonists of a given receptor form a cation-π interaction ...

Despite the mesocorticolimbic dopaminergic pathway being one of the main substrates underlying stimulating and reinforcing effects induced by psychostimulant drugs, there is little information regarding its role in their effects at the immune level. We have previously demonstrated that acute exposure to amphetamine (5mg/kg, i.p.) induced an inhibitory effect on ...

To investigate the difference in the dynamics of transforming growth factor β (TGF-β) receptors between normal and scleroderma fibroblasts. The cell surface expression levels of TGF-β receptors were determined by biotinylation and immunoprecipitation assay. The dynamics of TGF-β receptors on the cell surface was determined by the reversible biotinylation assay. ...

BACKGROUND: Randomized controlled trials and meta-analyses provide conflicting guidance on the role of beta-adrenergic receptor blockers (beta-blockers) in reducing perioperative complications. We hypothesize that variability in trial results may be due in part to heterogeneous properties of beta-blockers. First, we propose that the extent of beta-blocker metabolism by cytochrome P-450 ...

Our previous studies have demonstrated that bone morphogenetic protein 9 (BMP-9) is one of the most efficacious BMPs to induce osteoblast differentiation of mesenchymal stem cells (MSCs). However, the molecular mechanism underlying the BMP-9-induced osteogenic differentiation of MSCs remains to be fully elucidated. In this study, dominant negative (DN) type ...

Biased G protein-coupled receptor ligands engage subsets of the receptor signals normally stimulated by unbiased agonists. However, it is unclear whether ligand bias can elicit differentiated pharmacology in vivo. Here, we describe the discovery of a potent, selective β-arrestin biased ligand of the angiotensin II type 1 receptor. TRV120027 (Sar-Arg-Val-Tyr-Ile-His-Pro-D-Ala-OH) ...

β(2)-adrenergic receptors (β(2)-AR) are low abundance, integral membrane proteins that mediate the effects of catecholamines at the cell surface. Whereas the processes governing desensitization of activated β(2)-ARs and their subsequent removal from the cell surface have been characterized in considerable detail, little is known about the mechanisms controlling trafficking of ...

Inhaled beta(2) adrenoceptor (beta(2) AR) agonists are widely used as bronchodilator therapies for asthma and COPD. Different agonists have varying rates of onset of action, e.g. indacaterol and salbutamol are effective bronchodilators within 5 min whereas salmeterol takes 15 min to achieve significant bronchodilation over baseline (Brookman et al., Curr ...

The inhibitory Smads (I-Smads), i.e. Smad6 and Smad7, are negative regulators of transforming growth factor-β (TGF-β) family signaling. I-Smads inhibit TGF-β family signaling principally through physical interaction with type I receptors (activin receptor-like kinases), so as to compete with receptor-regulated Smads (R-Smads) for activation. However, how I-Smads interact with type ...

A dual goal for treating Alzheimer's disease (AD) is to decrease deposition of neurotoxic amyloid beta-peptide in the brain and to boost repair of damaged neurons. Donmez et al. (2010) now show that SIRT1 may mediate both processes by deacetylating the transcription factor retinoic acid receptor beta, a potential new ...

β-Arrestins, originally discovered to desensitize activated G protein-coupled receptors, (aka seven-transmembrane receptors, 7TMRs) also mediate 7TMR internalization and G protein-independent signaling via these receptors. More recently, several regulatory roles of β-arrestins for atypical 7TMRs and non-7TM receptors have emerged. Here, we uncover an entirely novel regulatory role of β-arrestins in ...

Transforming growth factor-β (TGF-β) binds with two transmembrane serine/threonine kinase receptors, type II (TβRII) and type I receptors (TβRI), and one accessory receptor, type III receptor (TβRIII), to transduce signals across cell membranes. Previous biochemical studies suggested that TβRI and TβRIII are preexisted homo-dimers. Using single-molecule microscopy to image green ...

GM-CSF, IL-3, and IL-5 are proinflammatory cytokines that control the production and function of myeloid and lymphoid cells. Their receptors are composed of a ligand-specific alpha subunit and a shared common signal-transducing beta subunit (beta common receptor or GM-CSFR beta [beta(c)]). The pleiotropic nature of biologic outcomes mediated by beta(c) ...

There are two important properties of receptor-ligand interactions: affinity (the ability of the ligand to bind to the receptor) and efficacy (the ability of the receptor-ligand complex to induce a response). Ligands are classified as agonists or antagonists depending on whether or not they have efficacy. In theory, it is ...

Responses and functions of airway epithelial cells are stimulated by β(2)-agonists via the β(2)-adrenergic receptors (β(2)-ARs)-G(s)-protein-cAMP-system, thus, affecting airway inflammation such as in asthma and equine recurrent airway obstruction (RAO). Though horses can be used as large animal model for human asthma, evaluation of the expression and functions of the ...

This review discusses the role of beta-alanine as a neurotransmitter. Beta-alanine is structurally intermediate between alpha-amino acid (glycine, glutamate) and gamma-amino acid (GABA) neurotransmitters. In general, beta-alanine satisfies a number of the prerequisite classical criteria for being a neurotransmitter: beta-alanine occurs naturally in the CNS, is released by electrical stimulation ...

Deoxynojirimycin (1) and two new related 4-O-hexosaminyl-containing disaccharide mimics, beta-d-TalNAc-(1-->4)-DNJ (4) and beta-d-ManNAc-(1-->4)-DNJ (5), have been studied as agonists of natural killer (NK) cell receptors. As a positive and unexpected result, DNJ (1) displayed a remarkable activation effect towards both NKR-P1A (rat) and CD69 (human) receptors, and a quite similar ...

The CB(1) cannabinoid receptor and the beta(2)-adrenoceptor are G protein-coupled receptors (GPCRs) co-expressed in many tissues. The present study examined physical and functional interactions between these receptors in a heterologous expression system and in primary human ocular cells. Physical interactions between CB(1) receptors and beta(2)-adrenoceptors were assessed using bioluminescence resonance ...

Following a lipophilicity-based hypothesis, an 8-hydroxyquinolinone 2-aminoindan derived series of beta(2)-adrenoceptor agonists have been prepared and evaluated for their potential as inhaled ultralong-acting bronchodilators. Determination of their activities at the human beta(2)-adrenoceptor receptor showed symmetrical substitution of the 2-aminoindan moiety at the 5- and 6-positions delivered the targeted intermediate potency ...

A major source of "high-output" NO in inflammation is inducible nitric oxide synthase (iNOS). iNOS is primarily transcriptionally regulated and is thought to function as an uncontrolled generator of high NO. We found that iNOS in cytokine-stimulated human lung microvascular endothelial cells (HLMVECs) is highly regulated post-translationally via activation of ...

CD40, a member of the tumour necrosis factor-alpha receptor family, is constitutively expressed by cells of haematopoietic and non-haematopoietic origin, including fibroblasts. Signalling through this receptor molecule regulates inflammatory mediator secretion by many cell types. The work has been performed in healthy subjects and the authors studied, by cellular culture, ...

Bone growth and remodeling depend upon the opposing rates of bone formation and resorption. These functions are regulated by intrinsic seven transmembrane-spanning receptors, the parathyroid hormone receptor (PTH1R) and frizzled (FZD), through their respective ligands, parathyroid hormone (PTH) and Wnt. FZD activation of canonical beta-catenin signaling requires the adapter protein ...

Transforming growth factor (TGF)-beta1, -beta2, and -beta3 are 25-kDa homodimeric polypeptides that play crucial nonoverlapping roles in embryogenesis, tissue development, carcinogenesis, and immune regulation. Here we report the 3.0-A resolution crystal structure of the ternary complex between human TGF-beta1 and the extracellular domains of its type I and type II ...

The internalization of beta(2)-adrenoceptors after agonist activation results in a desensitized and phosphorylated receptor that either resensitizes by recycling to the cell surface or becomes degraded by postendocytic sorting to lysosomes. The duration and physiological effects of agonists therefore depend on beta(2)-adrenoceptor sorting, highlighting the importance of sorting signals. Dileucine ...

The beta1- and beta2-adrenergic receptors (betaARs) on the surface of cardiomyocytes mediate distinct effects on cardiac function and the development of heart failure by regulating production of the second messenger cyclic adenosine monophosphate (cAMP). The spatial localization in cardiomyocytes of these betaARs, which are coupled to heterotrimeric guanine nucleotide-binding proteins ...

BACKGROUND: Glutamatergic neurotransmission has been implicated in mechanisms of alcohol-induced neurodegeneration and cognitive impairment, but the underlying mechanism remains unknown. Here, we examined whether the group II metabotropic glutamate receptor agonist LY379268 prevents neuronal death and learning deficits in a rat model of binge-like exposure to alcohol. METHODS: Following 4-day ...

The transforming growth factor-beta (TGF-beta) is part of a family of cytokines which regulate various signaling pathways such as cell development, growth, and tissue injury. Although several studies have been published describing the synthesis of small compounds which inhibit the receptor of TGF-beta, especially the subtype 1 receptor (TGBR1) kinase, ...

In this issue of Molecular Cell, Lee et al. (2010) show that the retinoic acid receptor-related orphan receptor alpha (RORalpha) can suppress the Wnt/beta-catenin signaling pathway in a Wnt5a- and PKC-dependent manner that does not alter beta-catenin stabilization or the recruitment of beta-catenin to Wnt target promoters.

Transforming growth factors-beta (TGF-betas) signal through type I and type II serine-threonine kinase receptor complexes. During ligand binding, type II receptors recruit and phosphorylate type I receptors, triggering downstream signaling. BAMBI [bone morphogenetic protein (BMP) and activin membrane-bound inhibitor] is a transmembrane pseudoreceptor structurally similar to type I receptors but ...

Animal models of anxiety disorders emphasize the crucial role of locus ceruleus-noradrenergic (norepinephrine, NE) signaling, the basolateral amygdala (BLA) and their interactions in the expression of anxiety-like behavioral responses to stress. Despite clinical evidence for the efficacy of a β-noradrenergic receptor blockade with propranolol in the alleviation of anxiety symptoms ...

Matrix remodeling, degradation, inflammation and invasion liberate peptide fragments that can subsequently interact with cells in an attachment-independent manner. Such 'soluble' matrix components, including collagens, fibronectin and laminin, induced Smad activation (termed crosstalk signaling), which follows a similar chronological sequence and R-Smad specificity as induced by transforming growth factor (TGF)-beta1. ...

The adrenergic receptors mediate a wide variety of physiological responses, including vasodilatation and vasoconstriction, heart rate modulation, and others. Beta-adrenergic antagonists ('beta-blockers') thus constitute a widely used class of drugs in cardiovascular medicine as well as in management of anxiety, migraine, and glaucoma. The importance of the hydrophobic effect has ...

beta-Arrestins, which were originally characterized as terminators of heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptor (GPCR) signaling, also act as important signal transducers. An emerging concept in GPCR signaling is beta-arrestin-biased agonism, in which specific ligand-activated GPCR conformational states selectively signal through beta-arrestins, rather than through G proteins. Here, we ...

Smad anchor for receptor activation (SARA) is known as Smad cofactor that interacts directly with Smad2/3 and functions to recruit Smad2/3 to the TGF-beta receptor. SARA plays an essential role in TGF-beta-induced Smad2 activation and it may modulate TGF-beta signaling through regulating the balance between Smad2 and Smad3. SARA also ...

Ubiquitously expressed seven-transmembrane receptors (7TMRs) classically signal through heterotrimeric G proteins and are commonly referred to as G protein-coupled receptors. It is now recognized that 7TMRs also signal through beta-arrestins, which act as versatile adapters controlling receptor signaling, desensitization, and trafficking. Most endogenous receptors appear to signal in a balanced ...

Trace amines, including tyramine, beta-phenylethylamine (beta-PEA), tryptamine and octopamine, are biologically active amines mostly based on phenylethylamine, occurring in the body in trace amounts. They are a diverse group of naturally occurring and synthetic amines, which are also found in the diet and in herbal plants, such as ephedrine and ...

In the present study the effects of bradykinin receptor antagonists were investigated in a murine model of asthma using BALB/c mice immunized with ovalbumin/alum and challenged twice with aerosolized ovalbumin. Twenty four hours later eosinophil proliferation in the bone marrow, activation (lipid bodies formation), migration to lung parenchyma and airways ...

GABA(A) receptors (GABAR) mediate most inhibition in the CNS and are also a target for neuroactive steroids such as 3alpha,5[alpha]beta-THP (3alphaOH-5[alpha]beta-OH-pregnan-20-one or [allo]pregnanolone). Although these steroids robustly enhance current gated by alpha1beta2delta GABAR, we have shown that 3alpha,5[alpha]beta-THP effects at recombinant alpha4beta2delta GABAR depend on the direction of Cl(-) flux, ...

Beta-2-Adrenergic receptors (beta(2)AR) participate in the physiologic responses of the lung, including bronchodilation and bronchoprotection, through mechanisms such as mucociliary clearance, fluid accumulation and mediator release from mast cells and basophils. Thus, these receptors may also play an important role in the pathophysiology of asthma. The gene encoding beta(2)AR (ADRB2) ...