Search results for " purine"
showing 10 items of 58 documents
The Guanine-Based Purinergic System: The Tale of An Orphan Neuromodulation.
2016
Guanine-based purines (GBPs) have been recently proposed to be not only metabolic agents but also extracellular signaling molecules that regulate important functions in the central nervous system. In such way, GBPs-mediated neuroprotection, behavioral responses and neuronal plasticity have been broadly described in the literature. However, while a number of these functions (i.e., GBPs neurothophic effects) have been well-established, the molecular mechanisms behind these GBPs-dependent effects are still unknown. Furthermore, no plasma membrane receptors for GBPs have been described so far, thus GBPs are still considered orphan neuromodulators. Interestingly, an intricate and controversial f…
Abacavir Induces Arterial Thrombosis in a Murine Model.
2018
Background The purinergic system is known to underlie prothrombotic and proinflammatory vascular programs, making the profile of experimental actions demonstrated by abacavir compatible with thrombogenesis. However, direct evidence of a prothrombotic effect by the drug has been lacking. Methods The present study appraised the effects of abacavir in a well-validated animal model of arterial thrombosis. The role of ATP-P2X7 receptors in the actions of the drug was also assessed, and the actions of recognized vascular-damaging agents and other nucleoside reverse-transcriptase inhibitors (NRTIs) were evaluated and compared to those of abacavir. Results Abacavir dose-dependently promoted thrombu…
Modulation of the TGF-β1-induced epithelial to mesenchymal transition (EMT) mediated by P1 and P2 purine receptors in MDCK cells
2017
Epithelial to mesenchymal transition (EMT) occurs during embryogenesis or under pathological conditions such as hypoxia, injury, chronic inflammation, or tissue fibrosis. In renal tubular epithelial cells (MDCK), TGF-β1 induces EMT by reducing or increasing epithelial or mesenchymal marker expression, respectively. In this study, we confirmed that the cAMP analogues, 8-CPT-cAMP or N6-Ph-cAMP, inhibited the TGF-β1-driven overexpression of the mesenchymal markers ZEB-1, Slug, Fibronectin, and α-SMA. Furthermore, we showed that A1, A2A, P2Y1, P2Y11, and P2X7 purine receptor agonists modulated the TGF-β1-induced EMT through the involvement of PKA and/or MAPK/ERK signaling. The stimulation o…
Ticagrelor, but not clopidogrel, reduces arterial thrombosis via endothelial tissue factor suppression
2017
The P2Y12 antagonist ticagrelor reduces mortality in patients with acute coronary syndrome (ACS), compared with clopidogrel, and the mechanisms underlying this effect are not clearly understood. Arterial thrombosis is the key event in ACS; however, direct vascular effects of either ticagrelor or clopidogrel with focus on arterial thrombosis and its key trigger tissue factor have not been previously investigated.Methods and results: Human aortic endothelial cells were treated with ticagrelor or clopidogrel active metabolite (CAM) and stimulated with tumour necrosis factor-alpha (TNF-α); effects on procoagulant tissue factor (TF) expression and activity, its counter-player TF pathway inhibito…
Tissue factor prothrombotic activity is regulated by integrin-arf6 trafficking
2017
Objective— Coagulation initiation by tissue factor (TF) is regulated by cellular inhibitors, cell surface availability of procoagulant phosphatidylserine, and thiol-disulfide exchange. How these mechanisms contribute to keeping TF in a noncoagulant state and to generating prothrombotic TF remain incompletely understood. Approach and Results— Here, we study the activation of TF in primary macrophages by a combination of pharmacological, genetic, and biochemical approaches. We demonstrate that primed macrophages effectively control TF cell surface activity by receptor internalization. After cell injury, ATP signals through the purinergic receptor P2rx7 induce release of TF + microvesicles. T…
Complex regional pain syndrome:intradermal injection of phenylephrine evokes pain and hyperalgesia in a subgroup of patients with upregulated α1-adre…
2018
The aim of this study was to determine whether upregulated cutaneous expression of α1-adrenoceptors (α1-AR) is a source of pain in patients with complex regional pain syndrome (CRPS). Immunohistochemistry was used to identify α1-AR on nerve fibres and other targets in the affected and contralateral skin of 90 patients, and in skin samples from 38 pain-free controls. The distribution of α1-AR was compared between patients and controls, and among subgroups of patients defined by CRPS duration, limb temperature asymmetry, and diagnostic subtype (CRPS I vs CRPS II). In addition, α1-AR expression was investigated in relation to pain and pinprick hyperalgesia evoked by intradermal injection of th…
Purinoceptor-mediated modulation by endogenous and exogenous agonists of stimulation-evoked [3H]noradrenaline release on rat iris.
1992
To investigate whether endogenous purinoceptor agonists affect the sympathetic neurotransmission in the rat isolated iris, and to classify the purinoceptors modulating exocytotic [3H]-noradrenaline release, we have determined the effect of adenosine receptor antagonists on, and the relative potency of selected agonists in modulating, the field stimulation-evoked (3 Hz, 2 min) [3H]-noradrenaline overflow. In addition, the apparent affinity constants of 8-phenyltheophylline (8-PT) and 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) in antagonizing the prejunctional effects of purinoceptor agonists were estimated. The relatively A1-selective DPCPX 10 and 100 nmol/l increased the evoked [3H]-noradre…
Pharmacological characterization of uracil nucleotide-preferring P2Y receptors modulating intestinal motility: a study on mouse ileum.
2011
We investigated the possible modulation of the intestinal contractility by uracil nucleotides (UTP and UDP), using as model the murine small intestine. Contractile activity of a mouse ileum longitudinal muscle was examined in vitro as changes in isometric tension. Transcripts encoding for uracil-sensitive receptors was investigated by RT-PCR. UDP induced muscular contractions, sensitive to PPADS, suramin, or MRS 2578, P2Y(6) receptor antagonist, and mimicked by PSB 0474, P2Y(6)-receptor agonist. UTP induced biphasic effects characterized by an early inhibition of the spontaneous contractile activity followed by muscular contraction. UTP excitatory effects were antagonized by PPADS, suramin,…
ATP and endogenous agonists inhibit evoked [3H]-noradrenaline release in rat iris via A1 and P2y-like purinoceptors.
1993
Effects of ATP, adenosine and purinoceptor antagonists on field stimulation-evoked (3 Hz, 2 min) [3H]-noradrenaline overflow were investigated in the rat isolated iris. ATP and adenosine inhibited the evoked overflow of [3H]-noradrenaline. 1,3-Dipropyl-8-cyclopentylxanthine (DPCPX) shifted the concentration-response curve of ATP to the right in a concentration-dependent manner, but with a potency (-log KB = 7.88) much lower than expected for an A1 adenosine receptor. In the continuous presence of DPCPX, the ATP-induced prejunctional inhibition was unaffected by suramin (100 mumol/l) and DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid, 50 mumol/l) but was antagonized by the P2Y-rece…
Evidence for the presence of P2y and P2x receptors with different functions in mouse stomach.
2005
To clarify the function of P2 receptor subtypes in mouse stomach, the motor responses to ATP, alpha,beta-methyleneATP (alpha,beta-MeATP), P2X receptor agonist, 2-methylthioATP (2-MeSATP), P2Y receptor agonist, and the effects of the desensitisation of P2X receptors with alpha,beta-MeATP and of P2Y receptors with ADPbetaS were analysed recording the endoluminal pressure from whole-organ. ATP-induced relaxation was antagonised by suramin, non-selective P2 receptor antagonist, by desensitisation of P2Y receptors with ADPbetaS, and increased by desensitisation of P2X receptors with alpha,beta-MeATP. alpha,beta-MeATP produced biphasic responses: relaxation, reduced by P2X- or P2Y desensitisation…