Identification of Lipid Mediators in Peripheral Human Tissues Using an Integrative In Vivo Microdialysis Approach

Abstract

Endocannabinoids and related N-acylethanolamines (NAEs) are lipid mediators involved in a number of physiological and pathological mechanisms in peripheral tissues. Microdialysis (MD) technique allows continues sampling of endogenous substances in the interstitial fluids of the tissues. The main limitation of MD sampling of lipophilic compounds is low recovery due to adsorption to the MD system and particularly to the catheter membranes. In this in vivo study microdialysate samples were collected from human trapezius muscle and forearm skin. The levels of arachidonoylethanolamide (AEA), 2-arachidonoylglycerol (2-AG), oleoylethanolamide (OEA), palmitoylethanolamide (PEA), and stearoylethanolamide (SEA) were analyzed in both microdialysate and in catheter membrane samples using liquid chromatography tandem mass spectrometry. OEA, PEA and SEA were identified in all microdialysate and catheter membrane samples from trapezius and skin. 2-AG was found in all catheter membrane samples from both tissues but not in the actual microdialysate. In conclusion sampling of OEA, PEA and SEA was achievable from trapezius and skin with the presented MD set-up. 2-AG is present in both trapezius muscle and skin tissue but adsorbs to the membranes in a higher extent than the NAEs. Furthermore, consideration of data conserved in the membrane during an MD experiment could be a relevant and more broadly applicable extension of MD sampling methodology which could fill an "information gap" and enhance an adequate interpretation of microdialysate data outcomes

Microvascular effects of insulin in the skin

“…It would also require insertion of numerous catheters in each subject, which ethically would be questionable. In a previous study in which endocannabinoids was studied in human muscle and skin, a similar dynamic adsorption pattern to the membrane was observed, with rapid initial adsorption followed by gradual detachment over time [134]. This indicates that there may be a need to not only let the tissue adapt to the catheter insertion, but also let the microdialysis system have time to stabilize and adapt before dialysate sampling is initiated.…”

Sampling insulin in different tissue compartments using microdialysis: methodological aspects

“…Relatively few studies have investigated adsorption to the microdialysis membrane (polyarylethersulphone). In Stensson et al 23 investigated the specific adsorption of endocannabinoids to the microdialysis membrane in vivo. Rather than having a static accumulation rate over time, a dynamic adsorption pattern of endocannabinoids to the membrane in muscle and skin was observed.…”

“…Similar to our study did the adsorption occur rapidly initially and relative adsorption decreased over time. The author's speculated whether the decrease in relative recovery could be due to tissue depletion of the analytes of interest 23 . No signs of depletion of insulin was however observed in this study ( Table 3).…”