Regulation of cerebromicrovascular permeability by lysophosphatidic acid

Hdl Handle:
http://hdl.handle.net/10149/95356
Title:
Regulation of cerebromicrovascular permeability by lysophosphatidic acid
Authors:
Sarker, M. H. (Mosharraf); Hu, D-E. (De-En); Fraser, P. A. (Paul)
Affiliation:
University of Teesside. School of Science and Engineering.
Citation:
Sarker, M. H., Hu, D-E. and Fraser, P. A. (2010) 'Regulation of cerebromicrovascular permeability by lysophosphatidic acid', Microcirculation, 17 (1), pp.39-46.
Publisher:
Taylor & Francis
Journal:
Microcirculation
Issue Date:
2010
URI:
http://hdl.handle.net/10149/95356
DOI:
10.1111/j.1549-8719.2010.00001.x
Abstract:
Objective: Lysophosphatidic acid (LPA) increases permeability of cerebral endothelium in culture, but it has been suggested that histamine release is required in vivo. Methods: Cerebral venular permeability was measured by using the single-vessel micro-occlusion technique, and fura-2 ratios were used to track changes in endothelial [Ca2+]. Results: Topical acute LPA application dose-dependently increased permeability (log EC50-9.4; similar to the K-d of the LPA1 receptor). The calcium response to LPA was similar to histamine, but the permeability response was unaffected by H-2-histamine receptor antagonism, and was blocked by Ki16425, a LPA1 receptor antagonist. The permeability response was blocked by nitric oxide synthase and free radical scavenging, which were carried out together, but not separately. Intravascular LPA bolus injection increased permeability. Whole serum albumin, or plasma albumin co-applied with LPA, increased permeability, but less potently than LPA itself (log EC50 5.1 and 6.1, respectively). Tachyphylaxis of the LPA1 receptor was demonstrated by LPA application for 10 minutes, which resulted in suppression of the response to subsequent applications for the following 15 minutes. Conclusions: Lysophosphatidic acid increases cerebrovascular permeability by acting directly on the endothelium and utilizes both nitric oxide and free radical signaling pathways.
Type:
Article
Language:
en
Keywords:
lysophosphatidic acid; capillary permeability; LPA1 receptor; brain; serum albumin
ISSN:
1073-9688; 1549-8719
Rights:
subject to 12 month embargo, author can archive post-print (ie final draft post-refereeing). For full details see http://www.sherpa.ac.uk/romeo/ [Accessed 31/03/2010]
Citation Count:
0 [Web of Science, 31/03/2010]

Full metadata record

DC FieldValue Language
dc.contributor.authorSarker, M. H. (Mosharraf)en
dc.contributor.authorHu, D-E. (De-En)en
dc.contributor.authorFraser, P. A. (Paul)en
dc.date.accessioned2010-03-31T11:23:52Z-
dc.date.available2010-03-31T11:23:52Z-
dc.date.issued2010-
dc.identifier.citationMicrocirculation; 17 (1): 39-46en
dc.identifier.issn1073-9688-
dc.identifier.issn1549-8719-
dc.identifier.doi10.1111/j.1549-8719.2010.00001.x-
dc.identifier.urihttp://hdl.handle.net/10149/95356-
dc.description.abstractObjective: Lysophosphatidic acid (LPA) increases permeability of cerebral endothelium in culture, but it has been suggested that histamine release is required in vivo. Methods: Cerebral venular permeability was measured by using the single-vessel micro-occlusion technique, and fura-2 ratios were used to track changes in endothelial [Ca2+]. Results: Topical acute LPA application dose-dependently increased permeability (log EC50-9.4; similar to the K-d of the LPA1 receptor). The calcium response to LPA was similar to histamine, but the permeability response was unaffected by H-2-histamine receptor antagonism, and was blocked by Ki16425, a LPA1 receptor antagonist. The permeability response was blocked by nitric oxide synthase and free radical scavenging, which were carried out together, but not separately. Intravascular LPA bolus injection increased permeability. Whole serum albumin, or plasma albumin co-applied with LPA, increased permeability, but less potently than LPA itself (log EC50 5.1 and 6.1, respectively). Tachyphylaxis of the LPA1 receptor was demonstrated by LPA application for 10 minutes, which resulted in suppression of the response to subsequent applications for the following 15 minutes. Conclusions: Lysophosphatidic acid increases cerebrovascular permeability by acting directly on the endothelium and utilizes both nitric oxide and free radical signaling pathways.en
dc.language.isoenen
dc.publisherTaylor & Francisen
dc.rightssubject to 12 month embargo, author can archive post-print (ie final draft post-refereeing). For full details see http://www.sherpa.ac.uk/romeo/ [Accessed 31/03/2010]en
dc.subjectlysophosphatidic aciden
dc.subjectcapillary permeabilityen
dc.subjectLPA1 receptoren
dc.subjectbrainen
dc.subjectserum albuminen
dc.titleRegulation of cerebromicrovascular permeability by lysophosphatidic aciden
dc.typeArticleen
dc.contributor.departmentUniversity of Teesside. School of Science and Engineering.en
dc.identifier.journalMicrocirculationen
ref.citationcount0 [Web of Science, 31/03/2010]en
or.citation.harvardSarker, M. H., Hu, D-E. and Fraser, P. A. (2010) 'Regulation of cerebromicrovascular permeability by lysophosphatidic acid', Microcirculation, 17 (1), pp.39-46.-
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