Characterization of biosynthesis and modes of action of prostaglandin E 2 and prostacyclin in guinea pig mesenteric lymphatic vessels

Abstract

Background and purpose: Rhythmical transient constrictions of the lymphatic vessels provide the means for efficient lymph drainage and interstitial tissue fluid balance. This activity is critical during inflammation, to avoid or limit oedema resulting from increased vascular permeability, mediated by the release of various inflammatory mediators. In this study, we investigated the mechanisms by which prostaglandin E 2 (PGE 2) and prostacyclin modulate lymphatic contractility in isolated guinea pig mesenteric lymphatic vessels. Experimental approach: Quantitative RT-PCR was used to assess the expression of mRNA for enzymes and receptors involved in the production and action of PGE 2 and prostacyclin in mesenteric collecting lymphatic vessels. Frequency and amplitude of lymphatic vessel constriction were measured in the presence of these prostaglandins and the role of their respective EP and IP receptors assessed. Key results: Prostaglandin E 2 and prostacyclin decreased concentration-dependently the frequency, without affecting the amplitude, of lymphatic constriction. Data obtained in the presence of the EP 4 receptor antagonists, GW627368x (1 μM) and AH23848B (30 μM) and the IP receptor antagonist CAY10441 (0.1 μM) suggest that PGE 2 predominantly activates EP 4, whereas prostacyclin mainly stimulates IP receptors. Inhibition of responses to either prostaglandin with H89 (10 μM) or glibenclamide (1 μM) suggested a role for the activation of protein kinase A and ATP-sensitive K + channels. Conclusions and implications: Our findings characterized the inhibition of lymphatic pumping induced by PGE 2 or prostacyclin in guinea pig mesenteric lymphatics. This action is likely to impair oedema resolution and to contribute to the pro-inflammatory actions of these prostaglandins. © 2009 The British Pharmacological Society All rights reserved.