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Signalling mechanisms in PAF-induced intestinal failure.

ABSTRACT: Capillary leakage syndrome, vasomotor disturbances and gut atony are common clinical problems in intensive care medicine. Various inflammatory mediators and signalling pathways are involved in these pathophysiological alterations among them platelet-activating factor (PAF). The related signalling mechanisms of the PAF-induced dysfunctions are only poorly understood. Here we used the model of the isolated perfused rat small intestine to analyse the role of calcium (using calcium deprivation, IP-receptor blockade (2-APB)), cAMP (PDE-inhibition plus AC activator), myosin light chain kinase (inhibitor ML-7) and Rho-kinase (inhibitor Y27632) in the following PAF-induced malfunctions: vasoconstriction, capillary and mucosal leakage, oedema formation, malabsorption and atony. Among these, the PAF-induced vasoconstriction and hyperpermeability appear to be governed by similar mechanisms that involve IP3 receptors, extracellular calcium and the Rho-kinase. Our findings further suggest that cAMP-elevating treatments - while effective against hypertension and oedema - bear the risk of dysmotility and reduced nutrient uptake. Agents such as 2-APB or Y27632, on the other hand, showed no negative side effects and improved most of the PAF-induced malfunctions suggesting that their therapeutic usefulness should be explored.

SUBMITTER: Lautenschlager I

PROVIDER: S-EPMC5645457 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Signalling mechanisms in PAF-induced intestinal failure.

Lautenschläger Ingmar I Wong Yuk Lung YL Sarau Jürgen J Goldmann Torsten T Zitta Karina K Albrecht Martin M Frerichs Inéz I Weiler Norbert N Uhlig Stefan S

Scientific reports 20171017 1

Capillary leakage syndrome, vasomotor disturbances and gut atony are common clinical problems in intensive care medicine. Various inflammatory mediators and signalling pathways are involved in these pathophysiological alterations among them platelet-activating factor (PAF). The related signalling mechanisms of the PAF-induced dysfunctions are only poorly understood. Here we used the model of the isolated perfused rat small intestine to analyse the role of calcium (using calcium deprivation, IP-r ...[more]

PMID: 29042668

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Signalling mechanisms in PAF-induced intestinal failure.

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Signalling mechanisms in PAF-induced intestinal failure.

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