The role of guanylyl cyclases in the permeability response to inflammatory mediators in pial venular capillaries in the rat

Hdl Handle:
http://hdl.handle.net/10149/99143
Title:
The role of guanylyl cyclases in the permeability response to inflammatory mediators in pial venular capillaries in the rat
Authors:
Sarker, M. H. (Mosharraf); Fraser, P. A. (Paul)
Affiliation:
King's College London. Centre for Cardiovascular Biology and Medicine.
Citation:
Sarker, M. H. and Fraser, P. A. (2002) 'The role of guanylyl cyclases in the permeability response to inflammatory mediators in pial venular capillaries in the rat', The Journal of Physiology, 540 (1), pp.209-218.
Publisher:
Wiley-Blackwell
Journal:
The Journal of Physiology
Issue Date:
1-Apr-2002
URI:
http://hdl.handle.net/10149/99143
DOI:
10.1113/jphysiol.2001.012912
Abstract:
Inflammatory mediators have a role in the formation of cerebral oedema and there is evidence that cGMP is an important signal in vascular permeability increase. We have investigated the role and the source of cGMP in mediating the permeability response to acutely applied bradykinin and the histamine H2 agonist dimaprit on single cerebral venular capillaries, by using the single vessel occlusion technique. We found that 8-bromo-cGMP applied acutely resulted in a small and reversible permeability increase with a log EC50 -7.2 ± 0.15 M. KT 5823, the inhibitor of cGMP-dependent protein kinase, abolished the permeability responses to both bradykinin and dimaprit, while zaprinast, an inhibitor of type 5 phosphodiesterase, potentiated the response to bradykinin. On the other hand, L-NMMA blocked the response to dimaprit, but not that to bradykinin. Inhibitors of soluble guanylyl cyclase, LY 85353 and methylene blue, also inhibited the permeability response to dimaprit, but not bradykinin. The permeability responses to thenatriuretic peptides ANP and CNP were of similar magnitude to that of bradykinin with log EC50 -10.0 ± 0.33 M and -8.7 ± 0.23 M, respectively. The natriuretic peptide receptor antagonist HS-142-1 blocked permeability responses to bradykinin as well as to ANP, and leukotriene D4 blocked the responses to CNP and bradykinin, but not to dimaprit. In conclusion, the histamine H2 receptor appears to signal via cGMP that is generated by a NO and soluble guanylyl cyclase, while bradykinin B2 receptor also signals via cGMP but through particulate guanylyl cyclase.
Type:
Article
Language:
en
Keywords:
guanylyl cyclases; permeability; inflammatory mediators; pial venular capillaries; rat
ISSN:
0022-3751
Rights:
Subject to restrictions, author can archive post-print (ie final draft post-refereeing). For full details see http://www.sherpa.ac.uk/romeo/ [Accessed 18/05/2010]
Citation Count:
13 [Scopus, 18/05/2010]

Full metadata record

DC FieldValue Language
dc.contributor.authorSarker, M. H. (Mosharraf)en
dc.contributor.authorFraser, P. A. (Paul)en
dc.date.accessioned2010-05-18T15:41:32Z-
dc.date.available2010-05-18T15:41:32Z-
dc.date.issued2002-04-01-
dc.identifier.citationThe Journal of Physiology; 540(1):209-218en
dc.identifier.issn0022-3751-
dc.identifier.doi10.1113/jphysiol.2001.012912-
dc.identifier.urihttp://hdl.handle.net/10149/99143-
dc.description.abstractInflammatory mediators have a role in the formation of cerebral oedema and there is evidence that cGMP is an important signal in vascular permeability increase. We have investigated the role and the source of cGMP in mediating the permeability response to acutely applied bradykinin and the histamine H2 agonist dimaprit on single cerebral venular capillaries, by using the single vessel occlusion technique. We found that 8-bromo-cGMP applied acutely resulted in a small and reversible permeability increase with a log EC50 -7.2 ± 0.15 M. KT 5823, the inhibitor of cGMP-dependent protein kinase, abolished the permeability responses to both bradykinin and dimaprit, while zaprinast, an inhibitor of type 5 phosphodiesterase, potentiated the response to bradykinin. On the other hand, L-NMMA blocked the response to dimaprit, but not that to bradykinin. Inhibitors of soluble guanylyl cyclase, LY 85353 and methylene blue, also inhibited the permeability response to dimaprit, but not bradykinin. The permeability responses to thenatriuretic peptides ANP and CNP were of similar magnitude to that of bradykinin with log EC50 -10.0 ± 0.33 M and -8.7 ± 0.23 M, respectively. The natriuretic peptide receptor antagonist HS-142-1 blocked permeability responses to bradykinin as well as to ANP, and leukotriene D4 blocked the responses to CNP and bradykinin, but not to dimaprit. In conclusion, the histamine H2 receptor appears to signal via cGMP that is generated by a NO and soluble guanylyl cyclase, while bradykinin B2 receptor also signals via cGMP but through particulate guanylyl cyclase.en
dc.language.isoenen
dc.publisherWiley-Blackwellen
dc.rightsSubject to restrictions, author can archive post-print (ie final draft post-refereeing). For full details see http://www.sherpa.ac.uk/romeo/ [Accessed 18/05/2010]en
dc.subjectguanylyl cyclasesen
dc.subjectpermeabilityen
dc.subjectinflammatory mediatorsen
dc.subjectpial venular capillariesen
dc.subjectraten
dc.titleThe role of guanylyl cyclases in the permeability response to inflammatory mediators in pial venular capillaries in the raten
dc.typeArticleen
dc.contributor.departmentKing's College London. Centre for Cardiovascular Biology and Medicine.en
dc.identifier.journalThe Journal of Physiologyen
ref.citationcount13 [Scopus, 18/05/2010]en
or.citation.harvardSarker, M. H. and Fraser, P. A. (2002) 'The role of guanylyl cyclases in the permeability response to inflammatory mediators in pial venular capillaries in the rat', The Journal of Physiology, 540 (1), pp.209-218.-
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