A single peri-sciatic nerve administration of the adenosine 2A receptor agonist ATL313 produces long-lasting anti-allodynia and anti-inflammatory effects in male rats

Kwilasz, Andrew J.; Fulgham, Suzanne M. Green; Ellis, Amanda; Patel, Hardik; Duran-Malle, Julissa Chante; Favret, Jacob; Harvey, Lewis O.; Rieger, Jayson M.; Maier, Steven F.; Watkins, Linda R.

doi:10.1016/j.bbi.2018.11.011

Cited by 17 publications

(3 citation statements)

References 52 publications

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“…Endogenous nitric oxide (NO) has been reported to promote mitokATP channel opening [30], and its inhibitor can block the cardioprotective effect induced by mitokATP channel inhibitor diazoxide [31]. A recent study found that A2a receptor agonist could suppress the expression of NO synthase protein, thus inhibited the release of NO [32]. In conclusion, A2aR may block the MitoKATP channels by decreasing the expression of NO.…”

Section: Dromparis Et Al Have Reported That the Mitochondrial-dependent Apoptotic Pathway Plays Anmentioning

confidence: 98%

Adenosine A2a Receptors Improve Hypoxic Pulmonary Arterial Hypertension Via Mitochondrial ATP-sensitive Potassium Channels

Cai

Zhang

et al. 2021

Arch Med Sci

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IntroductionThis study is aimed to explore the effects of Adenosine A2a receptors (A2aR) on hypoxia-induced pulmonary hypertension (HPH) via mitochondrial ATP-sensitive potassium channels (MitoKATP) in vivo and in vitro.Material and methodsUsing wild-type (WT) and A2aR-deficient (A2aR-/-) mice; hypoxic pulmonary artery smooth muscle cells (PASMCs) were induced by a 24-hours hypoxia exposure. Mice and PASMCs were treated with the A2aR agonist CGS21680, MitoKATP blocker 5-hydroxydecanoic acid sodium salt (5HD), or MitoKATP agonist diazoxide. Mitochondrial morphology was observed by electron microscopy. The mitochondrial membrane potential (Δψm); invasive hemodynamic parameters; right ventricular (RV) hypertrophy index; pulmonary arterial remodeling index; proliferative and apoptotic indexes; protein expression levels of A2aR, Bax, Bcl-2, and Caspase-9; and release of cytochrome C from the mitochondria to the cytoplasm were measured.ResultsIn vitro, hypoxia induced the opening of MitoKATP. The up-regulation of A2aR reduced the opening of MitoKATP, and the blocking of MitoKATP or activating A2aR promoted mitochondria-dependent apoptosis of PASMCs. In vivo, compared with WT mice, A2aR-/- mice displayed increased RV systolic pressure, RV hypertrophy index, and pulmonary arterial remodeling index. The expression levels of Bax, cytochrome C, and Caspase-9 were higher and Bcl-2 expression was lower in A2aR-/- mice than in WT mice. CGS21680 could reverse hypoxia-induced hemodynamic changes, RV hypertrophy, and pulmonary arterial remodeling as well as abnormal proliferation and apoptosis resistance in WT mice with pulmonary hypertension (PH).ConclusionsA2aR induced the mitochondrial-dependent apoptosis pathway and inhibited PASMC proliferation by blocking MitoKATP, thereby inhibiting pulmonary vascular structural remodeling and reducing PH.

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Section: Dromparis Et Al Have Reported That the Mitochondrial-dependent Apoptotic Pathway Plays Anmentioning

confidence: 98%

Adenosine A2a Receptors Improve Hypoxic Pulmonary Arterial Hypertension Via Mitochondrial ATP-sensitive Potassium Channels

Cai

Zhang

et al. 2021

Arch Med Sci

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“…Studies using A 2A ARs agonists delivered to the injured nerve site demonstrated effective suppression of neuropathic pain and neuroinflammation [ 17 ]. A single peri-sciatic nerve administration of the A 2A ARs agonist, ATL313, effectively suppressed ongoing neuropathic pain in rats [ 18 ]. This effect appears to be facilitated, at least in part, by the sustained activation of protein kinase A (PKA), the release of the anti-inflammatory cytokine interleukin (IL)-10, the decreased release of IL-1β and nitric oxide, as well as the reduced expression of markers associated with monocytes/macrophages.…”

Section: Ars In Cns Diseasesmentioning

confidence: 99%

Pharmacology of Adenosine Receptors: Recent Advancements

Vincenzi,

Pasquini,

Contri

et al. 2023

Biomolecules

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Adenosine receptors (ARs) are widely acknowledged pharmacological targets yet are still underutilized in clinical practice. Their ubiquitous distribution in almost all cells and tissues of the body makes them, on the one hand, excellent candidates for numerous diseases, and on the other hand, intrinsically challenging to exploit selectively and in a site-specific manner. This review endeavors to comprehensively depict the substantial advancements witnessed in recent years concerning the development of drugs that modulate ARs. Through preclinical and clinical research, it has become evident that the modulation of ARs holds promise for the treatment of numerous diseases, including central nervous system disorders, cardiovascular and metabolic conditions, inflammatory and autoimmune diseases, and cancer. The latest studies discussed herein shed light on novel mechanisms through which ARs exert control over pathophysiological states. They also introduce new ligands and innovative strategies for receptor activation, presenting compelling evidence of efficacy along with the implicated signaling pathways. Collectively, these emerging insights underscore a promising trajectory toward harnessing the therapeutic potential of these multifaceted targets.

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“…Следствием нарушения гематоневрального барьера явилось увеличение в эндоневрии макрофагов гематогенного происхождения. Для верификации макрофагов мы использовали маркер мононуклеарных фагоцитовбелок Iba-1, который экспрессируется в микроглиальных клетках центральной нервной системы [23], а также макрофагах периферических органов, в том числе периферического нерва [16,24]. В интактном нерве число макрофагов невелико: выявляется только популяция резидентных макрофагов.…”

Section: результатыunclassified

Morphological analysis of Wallerian degeneration in the rat sciatic nerve following mechanical damage

Petrova,

Kolos

2023

Clin. Exp. Morphology

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Introduction. Peripheral nerve injury is an important social problem. Fundamental research on mechanisms regulating degenerative and reparative processes that occur in the nerve following injury is necessary to find new ways of improving nerve regeneration. The purpose was to study the structural changes in the distal segment of the rat sciatic nerve at early stages following injury (ligature) using immunohistochemical and histochemical methods. Materials and methods. The rat sciatic nerve was subjected to mechanical trauma through ligation for a duration of 40 seconds. After days 7, 21, and 60, we analyzed changes in the nerve fibers using immunohistochemical reactions for alpha-tubulin and Luxol Fast Blue stains for myelin. Antibodies to tight junction protein claudin-1 were used to study perineurial cells. We identified Schwann cells (neurolemmocytes) and macrophages with the reaction for GFAP and the Iba-1 protein IHC reaction, respectively. Results. After 7 days, we observed degeneration of most nerve fibers, disintegration of myelin sheaths, disruption of the blood-neural barrier, migration of hematogenous macrophages, and dedifferentiation of Schwann cells in the endoneurium of the rat sciatic nerve distal segment. However, after day 21, the growth of nerve fibers from the proximal segment of the nerve and their remyelination were observed. The density of nerve fibers reached its highest value 60 days after the injury. Conclusion. We evaluated the relationship between the degree of myelin breakdown and the number of Iba-1+ macrophages, detected changes in the perineurium in the distal segment of the nerve, and identified dedifferentiated mitotically dividing Schwann cells. Keywords: Wallerian degeneration, damaged rat nerve, Luxol Fast Blue, claudin-1, Iba-1 protein, GFAP, immunohistochemistry

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A single peri-sciatic nerve administration of the adenosine 2A receptor agonist ATL313 produces long-lasting anti-allodynia and anti-inflammatory effects in male rats

Cited by 17 publications

References 52 publications

Adenosine A2a Receptors Improve Hypoxic Pulmonary Arterial Hypertension Via Mitochondrial ATP-sensitive Potassium Channels

Adenosine A2a Receptors Improve Hypoxic Pulmonary Arterial Hypertension Via Mitochondrial ATP-sensitive Potassium Channels

Pharmacology of Adenosine Receptors: Recent Advancements

Morphological analysis of Wallerian degeneration in the rat sciatic nerve following mechanical damage

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