The Experts below are selected from a list of 126 Experts worldwide ranked by ideXlab platform
M. H. Laughlin - One of the best experts on this subject based on the ideXlab platform.
-
The effect of Purinergic P2 Receptor blockade on skeletal muscle exercise hyperemia in miniature swine
European journal of applied physiology, 2014Co-Authors: Stefan P. Mortensen, Richard M. Mcallister, H T Yang, Ylva Hellsten, M. H. LaughlinAbstract:ATP could play an important role in skeletal muscle blood flow regulation by inducing vasodilation via Purinergic P2 Receptors. This study investigated the role of P2 Receptors in exercise hyperemia in miniature swine. We measured regional blood flow with radiolabeled-microsphere technique and systemic hemodynamics before and after arterial infusion of the P2 Receptor antagonist reactive blue 2 during treadmill exercise (5.2 km/h, ~60 % VO2max) and arterial ATP infusion in female Yucatan miniature swine (~29 kg). Mean blood flow during exercise from the 16 sampled skeletal muscle tissues was 138 ± 18 mL/min/100 g (mean ± SEM), and it was reduced in 11 (~25 %) of the 16 sampled skeletal muscles after RB2 was infused. RB2 also lowered diaphragm blood flow and kidney blood flow, whereas lung tissue blood flow was increased (all P
-
the effect of Purinergic P2 Receptor blockade on skeletal muscle exercise hyperemia in miniature swine
European Journal of Applied Physiology, 2014Co-Authors: Stefan P. Mortensen, Richard M. Mcallister, H T Yang, Ylva Hellsten, M. H. LaughlinAbstract:ATP could play an important role in skeletal muscle blood flow regulation by inducing vasodilation via Purinergic P2 Receptors. This study investigated the role of P2 Receptors in exercise hyperemia in miniature swine. We measured regional blood flow with radiolabeled-microsphere technique and systemic hemodynamics before and after arterial infusion of the P2 Receptor antagonist reactive blue 2 during treadmill exercise (5.2 km/h, ~60 % VO2max) and arterial ATP infusion in female Yucatan miniature swine (~29 kg). Mean blood flow during exercise from the 16 sampled skeletal muscle tissues was 138 ± 18 mL/min/100 g (mean ± SEM), and it was reduced in 11 (~25 %) of the 16 sampled skeletal muscles after RB2 was infused. RB2 also lowered diaphragm blood flow and kidney blood flow, whereas lung tissue blood flow was increased (all P < 0.05). Infusion of RB2 increased arterial lactate concentration during exercise from 1.6 ± 0.5 to 3.4 ± 0.6 mmol/L and heart rate from 216 ± 12 to 230 ± 9 beats/min, whereas blood pressure was unaltered. Arterial ATP infusion caused a ~twofold increase in blood flow in 15 of the 16 sampled muscle tissues and this effect was abolished after RB2 infusion. These results indicate that P2 Receptors play a role in regulating skeletal muscle blood flow during exercise in miniature swine.
Andreas Bringmann - One of the best experts on this subject based on the ideXlab platform.
-
P2Y1 Receptor Signaling Contributes to High Salt-Induced Priming of the NLRP3 Inflammasome in Retinal Pigment Epithelial Cells
PLOS ONE, 2016Co-Authors: Philipp Prager, Margrit Hollborn, Leon Kohen, Peter Wiedemann, Anja Steffen, Andreas BringmannAbstract:Background Systemic hypertension is a risk factor of age-related macular degeneration (AMD), a chronic inflammatory disease. Acute hypertension is caused by increased extracellular osmolarity after intake of dietary salt (NaCl). We determined in cultured human retinal pigment epithelial (RPE) cells whether high extracellular NaCl alters the gene expression of inflammasome-associated proteins, and whether autocrine/paracrine Purinergic (P2) Receptor signaling contributes to the NaCl-induced NLRP3 gene expression.
-
P2Y1 Receptor Signaling Contributes to High Salt-Induced Priming of the NLRP3 Inflammasome in Retinal Pigment Epithelial Cells
PLOS ONE, 2016Co-Authors: Philipp Prager, Margrit Hollborn, Leon Kohen, Peter Wiedemann, Anja Steffen, Andreas BringmannAbstract:Background Systemic hypertension is a risk factor of age-related macular degeneration (AMD), a chronic inflammatory disease. Acute hypertension is caused by increased extracellular osmolarity after intake of dietary salt (NaCl). We determined in cultured human retinal pigment epithelial (RPE) cells whether high extracellular NaCl alters the gene expression of inflammasome-associated proteins, and whether autocrine/paracrine Purinergic (P2) Receptor signaling contributes to the NaCl-induced NLRP3 gene expression.
-
early glial cell reactivity in experimental retinal detachment effect of suramin
Investigative Ophthalmology & Visual Science, 2003Co-Authors: Susann Uhlmann, Peter Wiedemann, Andreas Bringmann, Andreas Reichenbach, Ortrud Uckermann, Thomas Pannicke, Michael Weick, Elke Ulbricht, Iwona Goczalik, Mike FranckeAbstract:PURPOSE. In a rabbit model of retinal detachment, early Muller glial cell reactivity was monitored-specifically, changes in membrane features-to determine whether these changes involve an upregulation of Purinergic P2 Receptor-mediated responses and whether all or some of these alterations could be blocked by suramin or pyridoxal phosphate 6-azophenyl-2',4'-disulfonic acid (PPADS). In addition, the immune cell reactivity (microglial cells and blood-derived immune cells) was monitored. METHODS. A local retinal detachment was induced by subretinal injection of a sodium hyaluronate solution. Three, 24, 48, and 72 hours after surgery, Muller cells were acutely isolated, and patch-clamp records of the whole-cell potassium currents were made. The presence of P2 Receptor-mediated responses was determined by measuring extracellular adenosine triphosphate (ATP)-induced membrane current increases, and by recording of ATP-induced calcium responses at the vitreal surface of retinal wholemounts. The density of isolectin B 4 -labeled immune cells was determined in the nerve fiber layer of retinal wholemounts. RESULTS. Within 24 hours of detachment, Muller cell reactivity was evident. The cells downregulated the density of their inwardly rectifying potassium currents to 60% and 47% of the control value at 48 hours and 72 hours of detachment, respectively. This downregulation was accompanied by an enhanced incidence of cells which showed calcium and current responses after ATP application (control: 14%; 24 hours of detachment: 42%; 72 hours of detachment: 80%). Muller cell hypertrophy was apparent at 48 and 72 hours of detachment. Application of suramin during surgery inhibited the downregulation of potassium currents, but not the elevated responsiveness to extracellular ATP; PPADS had no effect. Suramin also inhibited the inflammatory response that was induced by the surgical procedure and that was apparent by the increased number of immune cells. CONCLUSIONS. Reactive responses of Muller cells occur within 24 hours of detachment. Suramin inhibits several (but not all) reactive glial alterations and therefore may represent one candidate for further investigations in the search for drugs that limit detrimental effects of immune cell activation and Muller cell gliosis during retinal detachment.
Peter Wiedemann - One of the best experts on this subject based on the ideXlab platform.
-
P2Y1 Receptor Signaling Contributes to High Salt-Induced Priming of the NLRP3 Inflammasome in Retinal Pigment Epithelial Cells
PLOS ONE, 2016Co-Authors: Philipp Prager, Margrit Hollborn, Leon Kohen, Peter Wiedemann, Anja Steffen, Andreas BringmannAbstract:Background Systemic hypertension is a risk factor of age-related macular degeneration (AMD), a chronic inflammatory disease. Acute hypertension is caused by increased extracellular osmolarity after intake of dietary salt (NaCl). We determined in cultured human retinal pigment epithelial (RPE) cells whether high extracellular NaCl alters the gene expression of inflammasome-associated proteins, and whether autocrine/paracrine Purinergic (P2) Receptor signaling contributes to the NaCl-induced NLRP3 gene expression.
-
P2Y1 Receptor Signaling Contributes to High Salt-Induced Priming of the NLRP3 Inflammasome in Retinal Pigment Epithelial Cells
PLOS ONE, 2016Co-Authors: Philipp Prager, Margrit Hollborn, Leon Kohen, Peter Wiedemann, Anja Steffen, Andreas BringmannAbstract:Background Systemic hypertension is a risk factor of age-related macular degeneration (AMD), a chronic inflammatory disease. Acute hypertension is caused by increased extracellular osmolarity after intake of dietary salt (NaCl). We determined in cultured human retinal pigment epithelial (RPE) cells whether high extracellular NaCl alters the gene expression of inflammasome-associated proteins, and whether autocrine/paracrine Purinergic (P2) Receptor signaling contributes to the NaCl-induced NLRP3 gene expression.
-
early glial cell reactivity in experimental retinal detachment effect of suramin
Investigative Ophthalmology & Visual Science, 2003Co-Authors: Susann Uhlmann, Peter Wiedemann, Andreas Bringmann, Andreas Reichenbach, Ortrud Uckermann, Thomas Pannicke, Michael Weick, Elke Ulbricht, Iwona Goczalik, Mike FranckeAbstract:PURPOSE. In a rabbit model of retinal detachment, early Muller glial cell reactivity was monitored-specifically, changes in membrane features-to determine whether these changes involve an upregulation of Purinergic P2 Receptor-mediated responses and whether all or some of these alterations could be blocked by suramin or pyridoxal phosphate 6-azophenyl-2',4'-disulfonic acid (PPADS). In addition, the immune cell reactivity (microglial cells and blood-derived immune cells) was monitored. METHODS. A local retinal detachment was induced by subretinal injection of a sodium hyaluronate solution. Three, 24, 48, and 72 hours after surgery, Muller cells were acutely isolated, and patch-clamp records of the whole-cell potassium currents were made. The presence of P2 Receptor-mediated responses was determined by measuring extracellular adenosine triphosphate (ATP)-induced membrane current increases, and by recording of ATP-induced calcium responses at the vitreal surface of retinal wholemounts. The density of isolectin B 4 -labeled immune cells was determined in the nerve fiber layer of retinal wholemounts. RESULTS. Within 24 hours of detachment, Muller cell reactivity was evident. The cells downregulated the density of their inwardly rectifying potassium currents to 60% and 47% of the control value at 48 hours and 72 hours of detachment, respectively. This downregulation was accompanied by an enhanced incidence of cells which showed calcium and current responses after ATP application (control: 14%; 24 hours of detachment: 42%; 72 hours of detachment: 80%). Muller cell hypertrophy was apparent at 48 and 72 hours of detachment. Application of suramin during surgery inhibited the downregulation of potassium currents, but not the elevated responsiveness to extracellular ATP; PPADS had no effect. Suramin also inhibited the inflammatory response that was induced by the surgical procedure and that was apparent by the increased number of immune cells. CONCLUSIONS. Reactive responses of Muller cells occur within 24 hours of detachment. Suramin inhibits several (but not all) reactive glial alterations and therefore may represent one candidate for further investigations in the search for drugs that limit detrimental effects of immune cell activation and Muller cell gliosis during retinal detachment.
-
Upregulation of extracellular ATP-induced Müller cell responses in a dispase model of proliferative vitreoretinopathy.
Investigative ophthalmology & visual science, 2002Co-Authors: Mike Francke, Ortrud Uckermann, Thomas Pannicke, Michael Weick, Iwona Goczalik, Jens Grosche, Ivan Milenkovic, S. Uhlmann, Frank Faude, Peter WiedemannAbstract:PURPOSE. To test whether in an animal model of proliferative vitreoretinopathy (PVR) the Muller glial cells displayed an up- regulation of Purinergic P2 Receptor-mediated responses. METHODS. PVR was induced by intravitreal injection of the proteolytic enzyme, dispase, in the eyes of adult rabbits. The developing PVR was examined ophthalmoscopically. After 3 weeks, small retinal pieces were wholemounted and used for calcium imaging, freshly dissociated Muller cells were sub- jected to calcium imaging, and patch-clamp recordings were made. The presence of P2 Receptor-mediated Ca 2 responses was determined both directly—that is, fluorometrically, and indirectly, by electrophysiological recording of Ca 2 -activated K currents. RESULTS. According to earlier observations in another model of retinal detachment and PVR, the reactive Muller cells displayed hypertrophy, downregulation of inwardly rectifying K cur- rents, and depolarization of the resting membrane potential, all dependent on the severity of the PVR. Further, significant PVR-induced increase was observed in the number of Muller cells responding to adenosine 5-triphosphate (ATP), with a transient elevation of their (Ca 2 )i. If isolated Muller cells were exposed to ATP, 13% of the control cells, but 29% (moderate PVR) or 53% (massive PVR) of the reactive cells, showed fluorometric Ca 2 increases. An increase of Ca 2 -activated K currents was measured in 11% of the control cells, but in 83%
Stefan P. Mortensen - One of the best experts on this subject based on the ideXlab platform.
-
The effect of Purinergic P2 Receptor blockade on skeletal muscle exercise hyperemia in miniature swine
European journal of applied physiology, 2014Co-Authors: Stefan P. Mortensen, Richard M. Mcallister, H T Yang, Ylva Hellsten, M. H. LaughlinAbstract:ATP could play an important role in skeletal muscle blood flow regulation by inducing vasodilation via Purinergic P2 Receptors. This study investigated the role of P2 Receptors in exercise hyperemia in miniature swine. We measured regional blood flow with radiolabeled-microsphere technique and systemic hemodynamics before and after arterial infusion of the P2 Receptor antagonist reactive blue 2 during treadmill exercise (5.2 km/h, ~60 % VO2max) and arterial ATP infusion in female Yucatan miniature swine (~29 kg). Mean blood flow during exercise from the 16 sampled skeletal muscle tissues was 138 ± 18 mL/min/100 g (mean ± SEM), and it was reduced in 11 (~25 %) of the 16 sampled skeletal muscles after RB2 was infused. RB2 also lowered diaphragm blood flow and kidney blood flow, whereas lung tissue blood flow was increased (all P
-
the effect of Purinergic P2 Receptor blockade on skeletal muscle exercise hyperemia in miniature swine
European Journal of Applied Physiology, 2014Co-Authors: Stefan P. Mortensen, Richard M. Mcallister, H T Yang, Ylva Hellsten, M. H. LaughlinAbstract:ATP could play an important role in skeletal muscle blood flow regulation by inducing vasodilation via Purinergic P2 Receptors. This study investigated the role of P2 Receptors in exercise hyperemia in miniature swine. We measured regional blood flow with radiolabeled-microsphere technique and systemic hemodynamics before and after arterial infusion of the P2 Receptor antagonist reactive blue 2 during treadmill exercise (5.2 km/h, ~60 % VO2max) and arterial ATP infusion in female Yucatan miniature swine (~29 kg). Mean blood flow during exercise from the 16 sampled skeletal muscle tissues was 138 ± 18 mL/min/100 g (mean ± SEM), and it was reduced in 11 (~25 %) of the 16 sampled skeletal muscles after RB2 was infused. RB2 also lowered diaphragm blood flow and kidney blood flow, whereas lung tissue blood flow was increased (all P < 0.05). Infusion of RB2 increased arterial lactate concentration during exercise from 1.6 ± 0.5 to 3.4 ± 0.6 mmol/L and heart rate from 216 ± 12 to 230 ± 9 beats/min, whereas blood pressure was unaltered. Arterial ATP infusion caused a ~twofold increase in blood flow in 15 of the 16 sampled muscle tissues and this effect was abolished after RB2 infusion. These results indicate that P2 Receptors play a role in regulating skeletal muscle blood flow during exercise in miniature swine.
Ylva Hellsten - One of the best experts on this subject based on the ideXlab platform.
-
The effect of Purinergic P2 Receptor blockade on skeletal muscle exercise hyperemia in miniature swine
European journal of applied physiology, 2014Co-Authors: Stefan P. Mortensen, Richard M. Mcallister, H T Yang, Ylva Hellsten, M. H. LaughlinAbstract:ATP could play an important role in skeletal muscle blood flow regulation by inducing vasodilation via Purinergic P2 Receptors. This study investigated the role of P2 Receptors in exercise hyperemia in miniature swine. We measured regional blood flow with radiolabeled-microsphere technique and systemic hemodynamics before and after arterial infusion of the P2 Receptor antagonist reactive blue 2 during treadmill exercise (5.2 km/h, ~60 % VO2max) and arterial ATP infusion in female Yucatan miniature swine (~29 kg). Mean blood flow during exercise from the 16 sampled skeletal muscle tissues was 138 ± 18 mL/min/100 g (mean ± SEM), and it was reduced in 11 (~25 %) of the 16 sampled skeletal muscles after RB2 was infused. RB2 also lowered diaphragm blood flow and kidney blood flow, whereas lung tissue blood flow was increased (all P
-
the effect of Purinergic P2 Receptor blockade on skeletal muscle exercise hyperemia in miniature swine
European Journal of Applied Physiology, 2014Co-Authors: Stefan P. Mortensen, Richard M. Mcallister, H T Yang, Ylva Hellsten, M. H. LaughlinAbstract:ATP could play an important role in skeletal muscle blood flow regulation by inducing vasodilation via Purinergic P2 Receptors. This study investigated the role of P2 Receptors in exercise hyperemia in miniature swine. We measured regional blood flow with radiolabeled-microsphere technique and systemic hemodynamics before and after arterial infusion of the P2 Receptor antagonist reactive blue 2 during treadmill exercise (5.2 km/h, ~60 % VO2max) and arterial ATP infusion in female Yucatan miniature swine (~29 kg). Mean blood flow during exercise from the 16 sampled skeletal muscle tissues was 138 ± 18 mL/min/100 g (mean ± SEM), and it was reduced in 11 (~25 %) of the 16 sampled skeletal muscles after RB2 was infused. RB2 also lowered diaphragm blood flow and kidney blood flow, whereas lung tissue blood flow was increased (all P < 0.05). Infusion of RB2 increased arterial lactate concentration during exercise from 1.6 ± 0.5 to 3.4 ± 0.6 mmol/L and heart rate from 216 ± 12 to 230 ± 9 beats/min, whereas blood pressure was unaltered. Arterial ATP infusion caused a ~twofold increase in blood flow in 15 of the 16 sampled muscle tissues and this effect was abolished after RB2 infusion. These results indicate that P2 Receptors play a role in regulating skeletal muscle blood flow during exercise in miniature swine.
