Endothelial cells cultured from human umbilical vein release ATP, substance P and acetylcholine in response to increased flow

Milner, P.; Kirkpatrick, Karen A.; Ralevic, Vera; Toothill, Valerie J.; Pearson, Jeremy D.; Burnstock, Geoffrey

doi:10.1098/rspb.1990.0092

Cited by 169 publications

(33 citation statements)

References 14 publications

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“…It has been shown that P2 activation leads to increases in concentration of intracellular calcium and PGE2 release (Naemsch et al, 2001). ATP, which activates this pathway, is typically released by bone, endothelial and epithelial cells and fibroblasts under stress conditions, acting as a DAMP/alarmin (Bodin & Burnstock, 1998;Burnstock, 1999;Furuya, Sokabe & Furuya, 2005;Grygorczyk & Hanrahan, 1997;John & Barakat, 2001;Katsuragi & Migita, 2004;Katz, Boland & Santillan, 2006;Kerkweg & de Groot, 2005;Milner et al, 1992;Milner et al, 1990b;Ohata et al, 1997;Patel et al, 2005;Romanello et al, 2001;Sauer, Hescheler & Wartenberg, 2000;Yamamoto et al, 2003).…”

Section: P2x7 Receptor: a Possible Mediator Of Orthodontic Mechanotramentioning

confidence: 99%

Orthodontic mechanotransduction and the role of the P2X7 receptor

Viecilli

Katona

Chen

et al. 2009

American Journal of Orthodontics and Dentofacial Orthopedics

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DEDICATIONTo my parents, who have supported my education. iv ACKNOWLEDGMENTSOne of the most important things I have learned during my PhD is the necessity of the existence of a working network of people that can help you achieve your goals. The more effectively this network functions, the higher the chance you will achieve the goals quickly.I would first like to thank my parents, who have unconditionally supported my decision to abandon a profitable private practice in Orthodontics, and return to humble student conditions while aiming for a full time academic career.I also thank my girlfriend Laura Kruter who has (almost always) been ok with my, some might say, not very sane ideas. Sometimes they do turn out fine, though (like this "PhD" one).I can hardly think of anyone else that could have complemented my work and ideas during this Program as well as Dr. Thomas Katona. While I was passionately conditioned to an idea, he was always rational and careful. While I was sometimes furious with a shortcoming, he was always temperate and humorous. When I ran into his office with some news about a project, he would always listen and almost never seem too busy to see me. While I was working and something went wrong, he would listen and wonder with me about the "whys" and "hows", instead of telling me what to do or express disappointment. He was even subject to some of my home culinary experiments. I was extremely fortunate to find someone that thought about science the same way I did, and that actually helped me with my project instead of just telling me what to do. I felt like we worked as a team, and that helped to increase my motivation during my studies. The third part of this project tested the role of the P2X7 receptor in the dentoalveolar morphology of C57B/6 mice. P2X7R KO (knockout) mice were compared to C57B/6 WT to identify differences in a maxillary molar and bone. Tooth dimensions viii were measured and 3D bone morphometry was conducted. No statistically significant differences were found between the two mouse types. P2X7R does not have a major effect on alveolar bone or tooth morphology.The final part examines the role of the P2X7 receptor in a controlled biomechanical model. Orthodontic mechanotransduction was compared in wild-type (WT) and P2X7R knock-out (KO) mice. Using Finite Element Analysis, mouse mechanics were scaled to produce typical human stress levels. Relationships between the biological responses and the calculated stresses were statistically tested and compared.There were direct relationships between certain stress magnitudes and root resorption and bone formation. Hyalinization and root and bone resorption were different in WT and KO. Orthodontic responses are related to the principal stress patterns in the PDL and the P2X7 receptor plays a significant role in their mechanotransduction.

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Section: P2x7 Receptor: a Possible Mediator Of Orthodontic Mechanotramentioning

confidence: 99%

Orthodontic mechanotransduction and the role of the P2X7 receptor

Viecilli

Katona

Chen

et al. 2009

American Journal of Orthodontics and Dentofacial Orthopedics

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“…It is known that fluid flow stimulates production of ATP by cultured EC (Milner et al, 1990) and the release rate is thought to increase with the applied wall shear stress (Yamamoto et al, 2003). Following John and Barakat (2001), we consider two possible production rate functions, both of which are increasing functions of wall shear stress, r w ( x): (11) where So, Tm ~ 0 are constants.…”

Section: Model For Atpmentioning

confidence: 99%

Atherosclerosis and calcium signalling in endothelial cells

Plank

Wall

Todem

2006

Progress in Biophysics and Molecular Biology

146

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The link between atherosclerosis and regions of disturbed flow and low wall shear stress is now firmly established, but the causal mechanisms underlying the link are not yet understood. It is now recognised that the endothelium is not simply a passive barrier between the blood and the vessel wall, but plays an active role in maintaining vascular homeostasis and participates in the onset of atherosclerosis. Calcium signalling is one of the principal intracellular signalling mechanisms by which endothelial cells (EC) respond to external stimuli, such as fluid shear stress and ligand binding. Previous studies have separately modelled mass transport of chemical species in the bloodstream and calcium dynamics in EC via the inositol triphosphate (IPa) signalling pathway. In this study, we integrate these two important components to provide an inclusive model for the calcium response of the endothelium in an arbitrary vessel geometry. This enables the combined effects of fluid flow and biochemical stimulation on EC to be investigated. Model results show that low endothelial calcium levels in the area of disturbed flow at an arterial widening may be one contributing factor to the onset of vascular disease.

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“…They also contain heterogeneous cytoplasmic stores of agonists that stimulate EDRF synthesis, including bradykinin, vasopressin, angiotensin II, 5-HT and substance P, although it is unclear whether these are taken up or synthesized de novo (Bodin, Bailey & Burnstock, 1991;Loesch, Bodin & Burnstock, 1991;Ralevic, Lincoln & Burnstock, 1992). Increases in flow stimulate release of ATP, and less consistently acetylcholine and substance P, from isolated endothelial cells, and substance P, vasopressin and ATP can be detected in the effluent from perfused rat hindlimb and rabbit brain preparations on increasing flow (Milner, Kirkpatrick, Ralevic, Toothill, Pearson & Burnstock, 1990;Ralevic, Milner, Hudlicka', Kristek & Burnstock, 1990;Domer, Alexander, Milner, Bodin & Burnstock, 1992). That ATP may be released in functionally active concentrations has been demonstrated in rat lung in which the consequences of flow-related ATP release are blocked by suramin, a P2 purinoreceptor antagonist, resulting in elevation of perfusion pressure (Hassessian, Bodin & Burnstock, 1993).…”

Section: Flow-induced Release Of Endothelium-dependent Agonistsmentioning

confidence: 99%

Modulation of blood flow and tissue perfusion by endothelium‐derived relaxing factor

Tm¹

1994

Experimental Physiology

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Endothelial cells cultured from human umbilical vein release ATP, substance P and acetylcholine in response to increased flow

Cited by 169 publications

References 14 publications

Orthodontic mechanotransduction and the role of the P2X7 receptor

Orthodontic mechanotransduction and the role of the P2X7 receptor

Atherosclerosis and calcium signalling in endothelial cells

Modulation of blood flow and tissue perfusion by endothelium‐derived relaxing factor

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