Breathing and the activity of its generator (the pre-Bötzinger complex; pre-BötC) are highly regulated functions. Among neuromodulators of breathing, somatostatin (SST) is unique: it is synthesized by a subset of glutamatergic pre-BötC neurons, but acts as an inhibitory neuromodulator. Moreover, SST regulates breathing both in normoxic and in hypoxic conditions. ...

Aims: To follow the IFNγ receptor expression on monocytes and granulocytes of cardiac surgical patients with respect to the type of cardiopulmonary bypass (CPB). METHODS: Expression of IFNγ receptor on monocytes and granulocytes of 26 cardiac surgical patients operated with the use of either "standard" or "miniaturised" CPB was determined ...

Ionotropic glutamate receptors (GluRs) are ligand-gated ion channels with a modular structure. The ion channel itself shares structural similarity, albeit an inverted membrane topology, with P-loop channels. Like P-loop channels, prokaryotic GluR subunits (e.g., GluR0) have two transmembrane segments. In contrast, eukaryotic GluRs have an additional transmembrane segment (M4), located ...

Choline is a micronutrient essential for the structural integrity of cellular membranes, and its presence at synapses follows either depolarization-induced pre-synaptic release or degradation of acetylcholine. Previous studies using whole-cell recording have shown that choline can modulate inhibitory input to hippocampal pyramidal neurons by acting upon nicotinic acetylcholine receptors (nAChRs) ...

Acute coronary syndrome (ACS) is a continuum of disease that includes non-ST-segment elevation ACS and ST-segment elevation myocardial infarction. The purpose of this article is to define the developing role of ticagrelor in ACS and compare it to currently available P2Y(12) receptor inhibitors. While clopidogrel remains the "workhorse" P2Y(12) receptor ...

Gram-negative sepsis carries high morbidity and mortality, especially when complicated by acute kidney injury (AKI). The mechanisms of AKI in sepsis remain poorly understood. Here we used intravital two-photon fluorescence microscopy to investigate the possibility of direct interactions between filtered endotoxin and tubular cells as a possible mechanism of AKI ...

In the caudal portions of the solitary tract (ST)nucleus, primary sensory afferents fall into two broad classes based on the expression of "Transient Receptor Potential Vanilloid Type 1" (TRPV1) receptors. Both afferent classes (TRPV1+/-) have indistinguishable glutamate release mechanisms for ST-evoked EPSCs. However, TRPV1+ terminals release additional glutamate from a ...

Deletion of a small cytoplasmic fragment close to the fourth transmembrane segment of the nicotinic α7 receptor (Glu437 to Arg447) abolished membrane expression. Different single mutants showed moderate to strong decreases in expression whereas the latter was totally abolished upon proline substitutions. We hypothesize that preservation of an α-helix formed ...

Serotonin 5-HT(6) receptor agonists and antagonists have been proposed as possible useful compounds in the treatment of psychiatric disorders such as depression. This study was aimed at characterizing ST 1936, a new 5-HT(6) receptor agonist, as a possible antidepressant/anti-anhedonic drug by studying its effects on two experimental models of depression. ...

PURPOSE: The purpose of this study was to identify whether leptin and connective tissue growth factor (CTGF) occur in the degenerative fibrocartilage disk and whether cartilage cells express leptin receptors. METHODS: The study included 23 patients diagnosed with degenerative articular disk tears of the triangular fibrocartilage (TFC) (Palmer type 2C). ...

In Fischer 344 (F344) rats, renin-angiotensin system (RAS) blockade for one year with the angiotensin II type 1 (AT(1)) receptor blocker L-158,809 prevents age-related impairments in metabolic function, similar to transgenic rats with low glial angiotensinogen (Aogen). Brain RAS regulation may contribute to the benefits of long-term systemic AT(1) antagonism. ...

To understand the physiological role of ghrelin, it is crucial to study both the actions of ghrelin and the regulation of ghrelin secretion. Although ghrelin actions have been extensively revealed, the direct factors regulating ghrelin secretion by ghrelin-producing cells (X/A-like cells), however, is not fully understood. In this study, we ...

The mu-opioid receptor encoded by the gene OPRM1 plays a primary role in opiate, alcohol, cocaine and nicotine addiction. Studies using opioid antagonists demonstrate that the mu-opioid receptor (MOP-r) also mediates the hypothalamic-pituitary-adrenal (HPA) axis stress response. A common polymorphism in exon one of the MOP-r gene, A118G, has been ...

Excitotoxic degeneration of spinal cord motoneurons has been proposed as a pathogenic mechanism in amyotrophic lateral sclerosis (ALS). Recently, we have reported that ghrelin, an endogenous ligand for growth hormone secretagogue receptor (GHS-R) 1a, functions as a neuroprotective factor in various animal models of neurodegenerative diseases. In this study, the ...

Present in vitro study in the wall lizard Hemidactylus flaviviridis, for the first time in ectothermic vertebrates, demonstrated the immunoregulatory role of neuropeptide Y (NPY) and its receptor-coupled downstream signaling cascade. NPY inhibited the percentage phagocytosis and phagocytic index of splenic phagocytes. The inhibitory effect of NPY on phagocytosis was ...

Dramatically up-regulated in the dorsal horn of the mammalian spinal cord following inflammation or nerve injury, neuropeptide Y (NPY) is poised to regulate the transmission of sensory signals. We found that doxycycline-induced conditional in vivo (Npy(tet/tet)) knockdown of NPY produced rapid, reversible, and repeatable increases in the intensity and duration ...

Cytokines, such as interferons, erythropoietin, leptin and most interleukins, signal through type 1 cytokine receptors and activate the canonical JAK-STAT pathway. Aberrant cytokine signalling underlies numerous pathologies and adequate, temporary receptor activation is therefore under tight control. Negative-feedback mechanisms are very well studied, but cellular sensitivity also depends on the ...

Based on the conformationally constrained DTrp-Phe-DTrp (wFw) core of the prototype inverse agonist [DArg1,DPhe5,DTrp7,9,Leu11]-substance P a series of novel, small peptide mimetic agonists for the ghrelin receptor were generated. By use of various simple, ring-constrained spacers connecting the DTrp-Phe-DTrp motif with the important C-terminal carboxyamide group, 40nM potency agonism was ...

The aim of this study was to evaluate by quantitative receptor autoradiography the interactions between Neuropeptide Y-Y1 (NPY Y1) and Galanin (GAL) receptors in the dorsal raphe nucleus (DRN) where both GAL receptors and NPY Y1 receptors exist. The ability of the GAL receptor antagonist M35 to block the GAL ...

Intracerebroventricular (ICV) administration of the octadecaneuropeptide (ODN), a peptide derived from diazepam-binding inhibitor (DBI), induces anorexigenic and anxiogenic-like actions in rodents. We have recently shown that, in goldfish, ICV injection of ODN also reduces food consumption via the metabotropic endozepine receptor. However, there is little information regarding the structure of ...

Recent studies have shown that leptin (an adipocytokine) played an important role in nociceptive behavior induced by nerve injury, but the cellular mechanism of this action remains unclear. Using the whole-cell patch-clamp recording from rat's spinal cord slices, we showed that superfusion of leptin onto spinal cord slices dose-dependently enhanced ...

The growth hormone(GH)/prolactin(PRL) family of polypeptide hormones plays important roles in many aspects of vertebrate physiology. In fish, there is an additional member in this family called somatolactin (SL). Specifically, zebrafish contains five ligands (GH, SLα, SLβ, PRL1 and PRL2) and four cognate receptors including two GH receptors (GHR1 and ...

Leptin is known to play a role in the modulation of metabolism and control of breathing acting mainly on central nervous structures, although additional actions on peripheral arterial chemoreceptors have also been suggested in the literature. We therefore examined by means of immunohistochemistry the expression of leptin and leptin receptors ...

When a child is not following the normal, predicted growth curve, an evaluation for underlying illnesses and central nervous system abnormalities is required and, appropriate consideration should be given to genetic defects causing GH deficiency (GHD). Because Insulin-like-Growth Factor-I (IGF-I) plays a pivotal role, GHD could also be considered as ...

Neuropeptide Y (NPY) and agouti-related peptide (AGRP) can produce hyperphagia, reduce energy expenditure, and promote triglyceride deposition in adipose depots. As these two neuropeptides are coexpressed within the hypothalamic arcuate nucleus and mediate a major portion of the obesity caused by leptin signaling deficiency, we sought to determine whether the ...

The present study investigates the mechanism by which obesity associated rise in leptin and insulin levels cause anovulation in vespertilionid bat, Scotophilus heathii. In the ovary of S. heathii, leptin and insulin receptors were mainly localized in interstitial and thecal cells and in the granulosa cells of primary follicles suggesting ...

The involvement of leptin in prostate diseases is related to an increase in the gene expression of both a and b isoform leptin receptors, leptin itself, androgen receptor, and aromatase, as well as by a reduction in both estrogen isoform receptors.

OBJECTIVE: Leptin and its receptor (Ob-R) are co-expressed in human placenta suggesting auto- and paracrine mechanisms of the hormone. So far it is unclear, how changes in the placental environment affect Ob-R expression. Hence, the main purpose of the study was to investigate leptin receptor expression and regulation under hypoxic ...

Melanocortin signalling is mediated by binding to a family of G protein-coupled receptors that positively couple to adenylyl cyclase. Tetrapod species have five melanocortin (MC(1)-MC(5)) receptors. The number of receptors varies in fish, zebrafish, for example, having six melanocortin receptors, with two copies of the melanocortin MC(5) receptor, while pufferfish ...

The objective of this study was to investigate the expression of leptin receptors in benign and malignant tumors of the ovaries and endometrium and its association with body mass index (BMI). Histological uterine and ovarian samples of normal and neoplastic tissue from 35 patients aged 37-72 years were examined for ...

We have recently clarified that nicotinic acetylcholine receptors (nAChRs) expressed in the thalamus play an important role in antiallodynic effects produced by the nAChR agonist, 5-iodo-3-(2(S)-azetidinylmethoxy)pyridine (5IA). This study aimed to reveal the in vivo relationship between thalamic nAChR occupancy rates and antiallodynic effects using 5IA and [¹²⁵I]5IA. We partially ...

Obesity is a growing epidemic characterized by excess fat storage in adipocytes. Although lipoprotein receptors play important roles in lipid uptake, their role in controlling food intake and obesity is not known. Here we show that the lipoprotein receptor LRP1 regulates leptin signaling and energy homeostasis. Conditional deletion of the ...

Increasing evidence indicates that the gut peptide ghrelin facilitates learning behavior and memory tasks. The present study demonstrates a cellular signaling mechanism of ghrelin in the hippocampus. Ghrelin stimulated CREB (cAMP response-element binding protein) through the activation of cAMP, protein kinase A (PKA), and PKA-dependent phosphorylation of NR1 subunit of ...

The possible role of leptin in colorectal tumors has been investigated in previous studies; however, to date, the conclusions remain under debate. Therefore, we investigated the serum leptin levels in colorectal adenoma patients. In addition, expression of the leptin receptor, and the leptin receptor-mediated signaling pathways were investigated in biopsy ...

The control of appetite and satiety is extremely complex and involves a balance between neurotransmitters and neuropeptides to stimulate and/or inhibit feeding behaviour. The effect of cannabinoids on food intake is well established, but little is known about the mechanism of action underlying their activity. In the present report, the ...

Leptin is an adipocytokine that links nutrition to immunity. Previous observation that a genetic polymorphism in the leptin receptor affected susceptibility to Entamoeba histolytica infection led to the hypothesis that leptin signaling has a protective role during intestinal amebic infection. In this study we show that mice lacking the functional ...

Leptin is a pleiotropic hormone acting both centrally and peripherally. It participates in a variety of biological processes, including energy metabolism, reproduction, and modulation of the immune response. So far, structural elements affecting leptin binding to its receptor remain unknown. We employed random mutagenesis of leptin, followed by selection of ...

Dose response curves for leptin facilitation of estrous behavior (lordosis and proceptivity) were made by infusing the peptide into the lateral ventricle (icv) of ovariectomized (ovx), ad libitum-fed rats injected 40h previously with 5μg of estradiol benzoate. Leptin doses of 1 and 3μg produced significant lordosis quotient at 60min post-injection, ...

We have previously identified that peripherally administered cholecystokinin (CCK) exerts an anorexigenic action via the vagal afferent, and subsequently the brain melanocortin- and corticotropin-releasing hormone-neuronal pathways in goldfish. N-Methyl-d-aspartate (NMDA) receptors have been shown to be involved in the regulations of locomotor activity and food intake in mammals. Although several ...

The α(7) nicotinic acetylcholine receptor (nAChR) is a potential therapeutic target for the treatment of cognitive deficits associated with schizophrenia, Alzheimer's disease, Parkinson's disease, and attention-deficit/hyperactivity disorder. Activation of α(7) nAChRs improved sensory gating and cognitive function in animal models and in early clinical trials. Here we describe the novel ...

In the sympathetic superior cervical ganglion (SCG), nicotinic acetylcholine receptors (nAChRs) mediate fast synaptic transmission. We previously demonstrated that in SCG neurons of mdx mice, an animal model for Duchenne muscular dystrophy, lack of dystrophin causes a decrease, compared to the wild-type, in post-synaptic nAChRs containing the α3 subunit associated ...

Leptin or obesity receptor (Ob-R) is a member of class I cytokine receptor family. Ob-R, expressed in six isoforms, is the product of alternative RNA splicing of db gene. According to its structural differences, the receptor's isoforms are divided into three classes: long, short, and secretory isoforms. A long, fully ...

The present work aimed to investigate whether and through which mechanisms selective α7 and α4β2 nicotinic receptor (nAChR) agonists stimulate endogenous glutamate (GLU) and aspartate (ASP) release in rat hippocampus. Rat hippocampal synaptosomes were purified on Percoll gradients and superfused in vitro to study endogenous GLU and ASP release. The ...

Tobacco smoking is considered to be one of the major risk factors for periodontitis. Nicotine, the major component in tobacco smoke, has been considered playing an important role in tobacco-related morbidity by acting through the nicotinic acetylcholine receptors (nAChRs) expressed by non-neuronal cells. Recently studies found that nAChRs could be ...

The aim of this study was to evaluate the antinociceptive effects and potential mechanisms of the spirocyclopiperazinium compound LXM-15. We found that LXM-15 produced significant antinociceptive effects in a dose- and time-dependent manner in mice. The maximum inhibition ratio was 70% in the acetic acid writhing test; the effect started ...

Antagonist activity at the α3β4 nicotinic acetylcholine receptor (nAChR) is thought to contribute to the antiaddictive properties of several compounds. However, truly selective ligands for the α3β4 nAChR have not been available. We report the discovery and SAR of a novel class of compounds that bind to the α3β4 nAChR ...

Nicotinic acetylcholine receptors (nAChR) in muscle fibers are densely packed in the postsynaptic region at the neuromuscular junction. Rapsyn plays a central role in directing and clustering nAChR during cellular differentiation and neuromuscular junction formation; however, it has not been demonstrated whether rapsyn is the only cause of receptor immobilization. ...

Modification of α-conotoxin frameworks through cyclization via an oligopeptide linker has previously been shown as an effective strategy for improving in vivo stability. We have extended this strategy by investigating cyclic analogs of α-conotoxin AuIB, a selective α(3)β(4) nicotinic acetylcholine receptor (nAChR) antagonist, to examine a range of oligopeptide linker ...

In order to advance therapeutic applications of nicotinic ligands, continuing research efforts are being directed toward the identification and characterization of novel nicotinic acetylcholine receptor (nAChR) ligands that are both potent and subtype selective. Herein we report the synthesis and pharmacological evaluation of members of a new series of 3-alkoxy-5-aminopyridine ...

Nicotinic acetylcholine receptors (nAChRs) are the binding sites for nicotinoid drugs, such as nicotine and epibatidine, and are the molecular targets of the selectively insecticidal neonicotinoids. In this study we report the full length cDNA cloning of the three Ctenocephalides (C.) felis (cat flea) nAChR α subunits Cfα1, Cfα2, and ...