Stimulation of adenosine receptor enhances α1 -adrenergic receptor-mediated activation of phospholipase C and Ca2+ mobilization in a pertussis toxin-sensitive manner in FRTL-5 thyroid cells

AbstractNorepinephrine (NE) stimulated FRTL-5 thyroid cells via an α1-adrenergic receptor, resulting in cytosolic Ca2+ ([Ca2+]i) mobilization and activation of phospholipase C. Adenosine and its receptor agonist, phenylisopropyladenosine (PIA), although not exerting a direct effect, markedly enhanced the NE-induced changes. Basal NE action was not totally abolished whereas the permissive action of adenosine and PIA was completely abolished by pretreatment of the cells with islet-activating protein (IAP), pertussis toxin. The decrease in cAMP level induced by adenosine or PIA is not the cause of their permissive effect, since this effect was not reversed by the addition of cAMP-increasing agents. We conclude that an IAP substrate GTP-binding protein(s) plays a novel role in forming a stimulatory coupling between an adenosine receptor and an α1-adrenergic receptor-coupled phospholipase C system

Ionotropic and metabotropic proton-sensing receptors involved in airway inflammation in allergic asthma

An acidic microenvironment has been shown to evoke a variety of airway responses, including cough, bronchoconstriction, airway hyperresponsiveness (AHR), infiltration of inflammatory cells in the lung, and stimulation of mucus hyperproduction. Except for the participation of transient receptor potential vanilloid-1 (TRPV1) and acid-sensing ion channels (ASICs) in severe acidic pH (of less than 6.0)-induced cough and bronchoconstriction through sensory neurons, the molecular mechanisms underlying extracellular acidic pH-induced actions in the airways have not been fully understood. Recent studies have revealed that ovarian cancer G protein-coupled receptor 1 (OGR1)-family G protein-coupled receptors, which sense pH of more than 6.0, are expressed in structural cells, such as airway smooth muscle cells and epithelial cells, and in inflammatory and immune cells, such as eosinophils and dendritic cells. They function in a variety of airway responses related to the pathophysiology of inflammatory diseases, including allergic asthma. In the present review, we discuss the roles of ionotropic TRPV1 and ASICs and metabotropic OGR1-family G protein-coupled receptors in the airway inflammation and AHR in asthma and respiratory diseases

Serum Apolipoprotein M Levels are Correlated with Biomarkers of Coagulation

Background:Apolipoprotein M (ApoM) is bound to high-density lipoprotein (HDL) in plasma, and HDL has anticoagulation effects. However, the association between ApoM and biomarkers of coagulation was unclear. Therefore, we investigated relationships between ApoM and biomarkers of coagulation. Methods: Serum samples from 233 Japanese participants including with diabetes mellitus, hypertension, dyslipidemia, or healthy controls were analyzed. Serum ApoM levels were measured using Enzyme-Linked Immuno-Sorbent Assay(ELISA). Results:Analysis of all 233 participants showed that ApoM levels were positively correlated with age (r＝0.284, p＜0.001), total cholesterol (TC;r＝0.477, p＜0.001), HDL-cholesterol (HDL-C;r＝0.234, p＜0.001) and lowdensity lipoprotein cholesterol (LDL-C;r＝0.331, p＜0.001). Higher ApoM levels were correlated with shorter activated partial thromboplastin time(APTT;r＝－0.226,p＝0.001) and prothrombin time(PT,％;r＝0.326,p＜ 0.001). Separate analysis of the 115 healthy controls showed that ApoM levels were positively correlated with age, TC, HDL-C and LDL-C, and higher ApoM levels were correlated with shorter PT. Conclusion:Serum levels of ApoM may influence biomarkers of coagulation

Mutations in the pH-Sensing G-protein-Coupled Receptor GPR68 Cause Amelogenesis Imperfecta

Amelogenesis is the process of dental enamel formation, leading to the deposition of the hardest tissue in the human body. This process requires the intricate regulation of ion transport and controlled changes to the developing enamel matrix pH. The means by which the enamel organ regulates pH during amelogenesis is largely unknown. We identified rare homozygous variants in GPR68 in three families with Amelogenesis Imperfecta, a genetically and phenotypically heterogeneous group of inherited conditions associated with abnormal enamel formation. Each of these homozygous variants (a large in-frame deletion, a frameshift deletion and a missense) were predicted to result in loss of function. GPR68 encodes a proton sensing G-protein-coupled receptor with sensitivity in the pH range that occurs in the developing enamel matrix during amelogenesis. Immunohistochemistry of rat mandibles confirmed localisation of GPR68 in the enamel organ at all stages of amelogenesis. Our data identify a role for GPR68 as a proton sensor that is required for proper enamel formation

Role of sphingosine 1-phosphate in anti-atherogenic actions of high-density lipoprotein

The reverse cholesterol transport mediated by high-density lipoprotein (HDL) is an important mechanism for maintaining body cholesterol, and hence, the crucial anti-atherogenic action of the lipoprotein. Recent studies, however, have shown that HDL exerts a variety of anti-inflammatory and anti-atherogenic actions independently of cholesterol metabolism. The present review provides an overview of the roles of sphingosine 1-phosphate (S1P)/S1P receptor and apolipoprotein A-I/scavenger receptor class B type I systems in the anti-atherogenic HDL actions. In addition, the physiological significance of the existence of S1P in the HDL particles is discussed

Synergism in cytosolic Ca2+ mobilization between bradykinin and agonists for pertussis toxin-sensitive G-protein-coupled receptors in NG 108-15 cells

AbstractBradykinin (BK) induced a transient and pertussis toxin (PT)-insensitive increase in cytosolic Ca2+ ([Ca2+]i) in NG 108-15 neuroblastoma × glioma hybrid cells, whereas leucine-enkephalin (EK), somatostatin, norepinephrine or carbachol showed a weak but PT-sensitive action. When any one of the latter agonists was applied to the cells treated with low doses of BK, however, the level of [Ca2+]i rise caused by the agonist was remarkably increased in a PT-sensitive manner. The decreasing of extracellular Ca2+ only slightly influenced the actions or these agonists. Thus, synergism between a BK receptor and PT-sensitive G-protein-coupled receptors results in marked intracellular Ca2+ mobilization by the latter agonists

Ionotropic and Metabotropic Proton-Sensing Receptors Involved in Airway Inflammation in Allergic Asthma

An acidic microenvironment has been shown to evoke a variety of airway responses, including cough, bronchoconstriction, airway hyperresponsiveness (AHR), infiltration of inflammatory cells in the lung, and stimulation of mucus hyperproduction. Except for the participation of transient receptor potential vanilloid-1 (TRPV1) and acid-sensing ion channels (ASICs) in severe acidic pH (of less than 6.0)-induced cough and bronchoconstriction through sensory neurons, the molecular mechanisms underlying extracellular acidic pH-induced actions in the airways have not been fully understood. Recent studies have revealed that ovarian cancer G protein-coupled receptor 1 (OGR1)-family G protein-coupled receptors, which sense pH of more than 6.0, are expressed in structural cells, such as airway smooth muscle cells and epithelial cells, and in inflammatory and immune cells, such as eosinophils and dendritic cells. They function in a variety of airway responses related to the pathophysiology of inflammatory diseases, including allergic asthma. In the present review, we discuss the roles of ionotropic TRPV1 and ASICs and metabotropic OGR1-family G protein-coupled receptors in the airway inflammation and AHR in asthma and respiratory diseases